Publications by authors named "Ernesto Pérez-Rueda"

62 Publications

An update of the unceasingly growing and diverse AraC/XylS family of transcriptional activators.

FEMS Microbiol Rev 2021 Apr 10. Epub 2021 Apr 10.

Laboratorio de Genética Microbiana, Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México, México.

Transcriptional factors play an important role in gene regulation in all organisms, especially in Bacteria. Here special emphasis is placed in the AraC/XylS family of transcriptional regulators. This is one of the most abundant as many predicted members have been identified and more members are added because more bacterial genomes are sequenced. Given the way more experimental evidence has mounded in the past decades, we decided to update the information about this captivating family of proteins. Using bioinformatics tools on all the data available for experimentally characterized members of this family, we found that many members that display a similar functional classification can be clustered together and in some cases they have a similar regulatory scheme. A proposal for grouping these proteins is also discussed. Additionally, an analysis of surveyed proteins in bacterial genomes is presented. Altogether, the current review presents a panoramic view into this family and we hope it helps to stimulate future research in the field.
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http://dx.doi.org/10.1093/femsre/fuab020DOI Listing
April 2021

A landscape for drug-target interactions based on network analysis.

PLoS One 2021 17;16(3):e0247018. Epub 2021 Mar 17.

Instituto de Investigaciones en Matemáticas Aplicadas y en Sistemas, Universidad Nacional Autónoma de México, Unidad Académica Yucatán, Mérida, Yucatán, México.

In this work, we performed an analysis of the networks of interactions between drugs and their targets to assess how connected the compounds are. For our purpose, the interactions were downloaded from the DrugBank database, and we considered all drugs approved by the FDA. Based on topological analysis of this interaction network, we obtained information on degree, clustering coefficient, connected components, and centrality of these interactions. We identified that this drug-target interaction network cannot be divided into two disjoint and independent sets, i.e., it is not bipartite. In addition, the connectivity or associations between every pair of nodes identified that the drug-target network is constituted of 165 connected components, where one giant component contains 4376 interactions that represent 89.99% of all the elements. In this regard, the histamine H1 receptor, which belongs to the family of rhodopsin-like G-protein-coupled receptors and is activated by the biogenic amine histamine, was found to be the most important node in the centrality of input-degrees. In the case of centrality of output-degrees, fostamatinib was found to be the most important node, as this drug interacts with 300 different targets, including arachidonate 5-lipoxygenase or ALOX5, expressed on cells primarily involved in regulation of immune responses. The top 10 hubs interacted with 33% of the target genes. Fostamatinib stands out because it is used for the treatment of chronic immune thrombocytopenia in adults. Finally, 187 highly connected sets of nodes, structured in communities, were also identified. Indeed, the largest communities have more than 400 elements and are related to metabolic diseases, psychiatric disorders and cancer. Our results demonstrate the possibilities to explore these compounds and their targets to improve drug repositioning and contend against emergent diseases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247018PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968663PMC
March 2021

Editorial: Systems Modeling: Approaches and Applications.

Front Mol Biosci 2020 9;7:620464. Epub 2020 Dec 9.

Departamento de Ingeniería Química y Bioprocesos, Pontificia Universidad Católica, Santiago, Chile.

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http://dx.doi.org/10.3389/fmolb.2020.620464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755927PMC
December 2020

Identification of L-asparaginases from strains with competitive activity and immunogenic profiles: a bioinformatic approach.

PeerJ 2020 13;8:e10276. Epub 2020 Nov 13.

Centro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México, Ensenada, Baja California, México.

The enzyme L-asparaginase from is a therapeutic enzyme that has been a cornerstone in the clinical treatment of acute lymphoblastic leukemia for the last decades. However, treatment effectiveness is limited by the highly immunogenic nature of the protein and its cross-reactivity towards L-glutamine. In this work, a bioinformatic approach was used to identify, select and computationally characterize L-asparaginases from through sequence-based screening analyses, immunoinformatics, homology modeling, and molecular docking studies. Based on its predicted low immunogenicity and excellent enzymatic activity, we selected a previously uncharacterized L-asparaginase from . Furthermore, two putative asparaginase binding sites were identified and a 3D model is proposed. These promising features allow us to propose L-asparaginase from as an alternative for the treatment of acute lymphocytic leukemia.
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http://dx.doi.org/10.7717/peerj.10276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668207PMC
November 2020

Gene Regulatory Networks of 2HH and 114-2 Inferred by a Computational Biology Approach.

Front Microbiol 2020 27;11:588263. Epub 2020 Oct 27.

Unidad Académica Yucatán, Instituto de Investigaciones en Matemáticas Aplicadas y en Sistemas, Universidad Nacional Autónoma de Mexico, Mérida, Mexico.

2HH and 114-2 are well-known cellulase fungal producers. However, few studies addressing global mechanisms for gene regulation of these two important organisms are available so far. A recent finding that the 2HH wild-type is closely related to leads to a combined study of these two species. Firstly, we provide a global gene regulatory network for 2HH and 114-2, based on TF-TG orthology relationships, considering three related species with well-known regulatory interactions combined with TFBSs prediction. The network was then analyzed in terms of topology, identifying TFs as hubs, and modules. Based on this approach, we explore numerous identified modules, such as the expression of cellulolytic and xylanolytic systems, where XlnR plays a key role in positive regulation of the xylanolytic system. It also regulates positively the cellulolytic system by acting indirectly through the cellodextrin induction system. This remarkable finding suggests that the XlnR-dependent cellulolytic and xylanolytic regulatory systems are probably conserved in both and . Finally, we explore the functional congruency on the genes clustered in terms of communities, where the genes related to cellular nitrogen, compound metabolic process and macromolecule metabolic process were the most abundant. Therefore, our approach allows us to confer a degree of accuracy regarding the existence of each inferred interaction.
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http://dx.doi.org/10.3389/fmicb.2020.588263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652724PMC
October 2020

The Microbial Composition in Circumneutral Thermal Springs from Chignahuapan, Puebla, Mexico Reveals the Presence of Particular Sulfur-Oxidizing Bacterial and Viral Communities.

Microorganisms 2020 Oct 29;8(11). Epub 2020 Oct 29.

Centro de Investigación en Dinámica Celular, Instituto de Investigación en Ciencias Básicas y Aplicadas, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Morelos, Mexico.

Terrestrial thermal springs are widely distributed globally, and these springs harbor a broad diversity of organisms of biotechnological interest. In Mexico, few studies exploring this kind of environment have been described. In this work, we explore the microbial community in Chignahuapan hot springs, which provides clues to understand these ecosystems' diversity. We assessed the diversity of the microorganism communities in a hot spring environment with a metagenomic shotgun approach. Besides identifying similarities and differences with other ecosystems, we achieved a systematic comparison against 11 metagenomic samples from diverse localities. The Chignahuapan hot springs show a particular prevalence of sulfur-oxidizing bacteria from the genera , , , , , and , highlighting those that are different from other recovered bacterial populations in circumneutral hot springs environments around the world. The co-occurrence analysis of the bacteria and viruses in these environments revealed that within the , , , and genera, the Chignahuapan samples have specific species of bacteria with a particular abundance, such as . The viruses in the circumneutral hot springs present bacteriophages within the order Caudovirales (Siphoviridae, Myoviridae, and Podoviridae), but the family of Herelleviridae was the most abundant in Chignahuapan samples. Furthermore, viral auxiliary metabolic genes were identified, many of which contribute mainly to the metabolism of cofactors and vitamins as well as carbohydrate metabolism. Nevertheless, the viruses and bacteria present in the circumneutral environments contribute to the sulfur cycle. This work represents an exhaustive characterization of a community structure in samples collected from hot springs in Mexico and opens opportunities to identify organisms of biotechnological interest.
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http://dx.doi.org/10.3390/microorganisms8111677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692377PMC
October 2020

Deciphering the functional diversity of DNA-binding transcription factors in Bacteria and Archaea organisms.

PLoS One 2020 21;15(8):e0237135. Epub 2020 Aug 21.

Instituto de Investigaciones en Matemáticas Aplicadas y en Sistemas, Universidad Nacional Autónoma de México, Unidad Académica Yucatán, Mérida, Yucatán, México.

DNA-binding Transcription Factors (TFs) play a central role in regulation of gene expression in prokaryotic organisms, and similarities at the sequence level have been reported. These proteins are predicted with different abundances as a consequence of genome size, where small organisms contain a low proportion of TFs and large genomes contain a high proportion of TFs. In this work, we analyzed a collection of 668 experimentally validated TFs across 30 different species from diverse taxonomical classes, including Escherichia coli K-12, Bacillus subtilis 168, Corynebacterium glutamicum, and Streptomyces coelicolor, among others. This collection of TFs, together with 111 hidden Markov model profiles associated with DNA-binding TFs collected from diverse databases such as PFAM and DBD, was used to identify the repertoire of proteins putatively devoted to gene regulation in 1321 representative genomes of Archaea and Bacteria. The predicted regulatory proteins were posteriorly analyzed in terms of their genomic context, allowing the prediction of functions for TFs and their neighbor genes, such as genes involved in virulence, enzymatic functions, phosphorylation mechanisms, and antibiotic resistance. The functional analysis associated with PFAM groups showed diverse functional categories were significantly enriched in the collection of TFs and the proteins encoded by the neighbor genes, in particular, small-molecule binding and amino acid transmembrane transporter activities associated with the LysR family and proteins devoted to cellular aromatic compound metabolic processes or responses to drugs, stress, or abiotic stimuli in the MarR family. We consider that with the increasing data derived from new technologies, novel TFs can be identified and help improve the predictions for this class of proteins in complete genomes. The complete collection of experimentally characterized and predicted TFs is available at http://web.pcyt.unam.mx/EntrafDB/.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237135PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446807PMC
October 2020

Evaluation of the Abundance of DNA-Binding Transcription Factors in Prokaryotes.

Genes (Basel) 2020 01 3;11(1). Epub 2020 Jan 3.

Instituto de Investigaciones en Matemáticas Aplicadas y en Sistemas, Universidad Nacional Autónoma de México, Unidad Académica Yucatán, Mérida.C.P. 97302, Yucatán, Mexico.

The ability of bacteria and archaea to modulate metabolic process, defensive response, and pathogenic capabilities depend on their repertoire of genes and capacity to regulate the expression of them. Transcription factors (TFs) have fundamental roles in controlling these processes. TFs are proteins dedicated to favor and/or impede the activity of the RNA polymerase. In prokaryotes these proteins have been grouped into families that can be found in most of the different taxonomic divisions. In this work, the association between the expansion patterns of 111 protein regulatory families was systematically evaluated in 1351 non-redundant prokaryotic genomes. This analysis provides insights into the functional and evolutionary constraints imposed on different classes of regulatory factors in bacterial and archaeal organisms. Based on their distribution, we found a relationship between the contents of some TF families and genome size. For example, nine TF families that represent 43.7% of the complete collection of TFs are closely associated with genome size; i.e., in large genomes, members of these families are also abundant, but when a genome is small, such TF family sizes are decreased. In contrast, almost 102 families (56.3% of the collection) do not exhibit or show only a low correlation with the genome size, suggesting that a large proportion of duplication or gene loss events occur independently of the genome size and that various yet-unexplored questions about the evolution of these TF families remain. In addition, we identified a group of families that have a similar distribution pattern across and , suggesting common functional and probable coevolution processes, and a group of families universally distributed among all the genomes. Finally, a specific association between the TF families and their additional domains was identified, suggesting that the families sense specific signals or make specific protein-protein contacts to achieve the regulatory roles.
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http://dx.doi.org/10.3390/genes11010052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017128PMC
January 2020

Identification of Modules With Similar Gene Regulation and Metabolic Functions Based on Co-expression Data.

Front Mol Biosci 2019 13;6:139. Epub 2019 Dec 13.

Instituto de Investigaciones en Matemáticas Aplicadas y en Sistemas, Universidad Nacional Autónoma de México, Unidad Académica Yucatán, Mérida, Mexico.

Biological systems respond to environmental perturbations and to a large diversity of compounds through gene interactions, and these genetic factors comprise complex networks. In particular, a wide variety of gene co-expression networks have been constructed in recent years thanks to the dramatic increase of experimental information obtained with techniques, such as microarrays and RNA sequencing. These networks allow the identification of groups of co-expressed genes that can function in the same process and, in turn, these networks may be related to biological functions of industrial, medical and academic interest. In this study, gene co-expression networks for 17 bacterial organisms from the COLOMBOS database were analyzed via weighted gene co-expression network analysis and clustered into modules of genes with similar expression patterns for each species. These networks were analyzed to determine relevant modules through a hypergeometric approach based on a set of transcription factors and enzymes for each genome. The richest modules were characterized using PFAM families and KEGG metabolic maps. Additionally, we conducted a Gene Ontology analysis for enrichment of biological functions. Finally, we identified modules that shared similarity through all the studied organisms by using comparative genomics.
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http://dx.doi.org/10.3389/fmolb.2019.00139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929668PMC
December 2019

The protein architecture in Bacteria and Archaea identifies a set of promiscuous and ancient domains.

PLoS One 2019 19;14(12):e0226604. Epub 2019 Dec 19.

Instituto de Investigaciones en Matemáticas Aplicadas y en Sistemas, Universidad Nacional Autónoma de México, Unidad Académica Yucatán, Mérida, Yucatán, México.

In this work, we describe a systematic comparative genomic analysis of promiscuous domains in genomes of Bacteria and Archaea. A quantitative measure of domain promiscuity, the weighted domain architecture score (WDAS), was used and applied to 1317 domains in 1320 genomes of Bacteria and Archaea. A functional analysis associated with the WDAS per genome showed that 18 of 50 functional categories were identified as significantly enriched in the promiscuous domains; in particular, small-molecule binding domains, transferases domains, DNA binding domains (transcription factors), and signal transduction domains were identified as promiscuous. In contrast, non-promiscuous domains were identified as associated with 6 of 50 functional categories, and the category Function unknown was enriched. In addition, the WDASs of 52 domains correlated with genome size, i.e., WDAS values decreased as the genome size increased, suggesting that the number of combinations at larger domains increases, including domains in the superfamilies Winged helix-turn-helix and P-loop-containing nucleoside triphosphate hydrolases. Finally, based on classification of the domains according to their ancestry, we determined that the set of 52 promiscuous domains are also ancient and abundant among all the genomes, in contrast to the non-promiscuous domains. In summary, we consider that the association between these two classes of protein domains (promiscuous and non-promiscuous) provides bacterial and archaeal cells with the ability to respond to diverse environmental challenges.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226604PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6922389PMC
April 2020

Intermediate-Salinity Systems at High Altitudes in the Peruvian Andes Unveil a High Diversity and Abundance of Bacteria and Viruses.

Genes (Basel) 2019 11 5;10(11). Epub 2019 Nov 5.

Centro de Investigación en Dinámica Celular, Instituto de Investigación en Ciencias Básicas y Aplicadas, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos C.P. 62209, Mexico.

Intermediate-salinity environments are distributed around the world. Here, we present a snapshot characterization of two Peruvian thalassohaline environments at high altitude, Maras and Acos, which provide an excellent opportunity to increase our understanding of these ecosystems. The main goal of this study was to assess the structure and functional diversity of the communities of microorganisms in an intermediate-salinity environment, and we used a metagenomic shotgun approach for this analysis. These Andean hypersaline systems exhibited high bacterial diversity and abundance of the phyla , , , and ; in contrast, from the phyla , , and were identified in low abundance. Acos harbored a more diverse prokaryotic community and a higher number of unique species compared with Maras. In addition, we obtained the draft genomes of two bacteria, and , as well as the viral genomes of lambda-like phage and -like phage and 27 partial novel viral halophilic genomes. The functional metagenome annotation showed a high abundance of sequences associated with detoxification, DNA repair, cell wall and capsule formation, and nucleotide metabolism; sequences for these functions were overexpressed mainly in bacteria and also in some archaea and viruses. Thus, their metabolic profiles afford a decrease in oxidative stress as well as the assimilation of nitrogen, a critical energy source for survival. Our work represents the first microbial characterization of a community structure in samples collected from Peruvian hypersaline systems.
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http://dx.doi.org/10.3390/genes10110891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895999PMC
November 2019

Identification of functional signatures in the metabolism of the three cellular domains of life.

PLoS One 2019 28;14(5):e0217083. Epub 2019 May 28.

Instituto de Investigaciones en Matemáticas Aplicadas y en Sistemas, Universidad Nacional Autónoma de México, Unidad Académica Yucatán, Mérida, Yucatán, México.

In order to identify common and specific enzymatic activities associated with the metabolism of the three cellular domains of life, the conservation and variations between the enzyme contents of Bacteria, Archaea, and Eukarya organisms were evaluated. To this end, the content of enzymes belonging to a particular pathway and their abundance and distribution in 1507 organisms that have been annotated and deposited in the KEGG database were assessed. In addition, we evaluated the consecutive enzymatic reaction pairs obtained from metabolic pathway reactions and transformed into sequences of enzymatic reactions, with catalytic activities encoded in the Enzyme Commission numbers, which are linked by a substrate. Both analyses are complementary: the first considers individual reactions associated with each organism and metabolic map, and the second evaluates the functional associations between pairs of consecutive reactions. From these comparisons, we found a set of five enzymatic reactions that were widely distributed in all the organisms and considered here as universal to Bacteria, Archaea, and Eukarya; whereas 132 pairs out of 3151 reactions were identified as significant, only 5 of them were found to be widely distributed in all the taxonomic divisions. However, these universal reactions are not widely distributed along the metabolic maps, suggesting their dispensability to all metabolic processes. Finally, we found that universal reactions are also associated with ancestral domains, such as those related to phosphorus-containing groups with a phosphate group as acceptor or those related to the ribulose-phosphate binding barrel, triosephosphate isomerase, and D-ribose-5-phosphate isomerase (RpiA) lid domain, among others. Therefore, we consider that this analysis provides clues about the functional constraints associated with the repertoire of enzymatic functions per organism.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0217083PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538242PMC
January 2020

Dissecting the Repertoire of DNA-Binding Transcription Factors of the Archaeon Pyrococcus furiosus DSM 3638.

Life (Basel) 2018 Sep 21;8(4). Epub 2018 Sep 21.

Instituto de Investigaciones en Matemáticas Aplicadas y en Sistemas, Universidad Nacional Autónoma de México, Unidad Académica Yucatán, C.P. 97302, Mérida, Yucatán, Mexico.

In recent years, there has been a large increase in the amount of experimental evidence for diverse archaeal organisms, and these findings allow for a comprehensive analysis of archaeal genetic organization. However, studies about regulatory mechanisms in this cellular domain are still limited. In this context, we identified a repertoire of 86 DNA-binding transcription factors (TFs) in the archaeon DSM 3638, that are clustered into 32 evolutionary families. In structural terms, 45% of these proteins are composed of one structural domain, 41% have two domains, and 14% have three structural domains. The most abundant DNA-binding domain corresponds to the winged helix-turn-helix domain; with few alternative DNA-binding domains. We also identified seven regulons, which represent 13.5% (279 genes) of the total genes in this archaeon. These analyses increase our knowledge about gene regulation in DSM 3638 and provide additional clues for comprehensive modeling of transcriptional regulatory networks in the cellular domain.
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http://dx.doi.org/10.3390/life8040040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6316755PMC
September 2018

Functional Prediction of Hypothetical Transcription Factors of K-12 Based on Expression Data.

Comput Struct Biotechnol J 2018 27;16:157-166. Epub 2018 Mar 27.

Instituto de Investigaciones en Matemáticas Aplicadas y en Sistemas, Universidad Nacional Autónoma de México, Unidad Académica Yucatán, C.P. 97302 Mérida, Yucatán, Mexico.

The repertoire of 304 DNA-binding transcription factors (TFs) in K-12 has been described recently, with 196 TFs experimentally characterized and 108 proteins predicted by sequence comparisons. Based on 303 expression profile patterns retrieved from the Colombos database 12 clusters were identified, including hypothetical and experimentally characterized TFs, using a spectral clustering algorithm based on a 3NN graph built using 14 principal components that represent 65% of the variance of the expression data. In a posterior step, clusters were characterized in terms of their associated overrepresented functions, based on KEGG, Supfam annotations and Pfam assignments among other functional categories using an enrichment test, reinforcing the notion that the identified clusters are functionally similar among them. Based on these data, the we identified 12 clusters in which hypothetical and known TFs share similar regulatory and physiological functions, such as module associations of toxin-antitoxin (TA) systems with DNA repair mechanisms, amino acid biosynthesis, and carbon metabolism/transport, among others. This analysis has increased our knowledge about gene regulation in K-12 and can be further expanded to other organisms.
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http://dx.doi.org/10.1016/j.csbj.2018.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055005PMC
March 2018

Genome misclassification of Klebsiella variicola and Klebsiella quasipneumoniae isolated from plants, animals and humans.

Salud Publica Mex 2018 Jan-Feb;60(1):56-62

Grupo de Resistencia Bacteriana, Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública. Cuernavaca, Morelos, México.

Objective: Due to the fact that K. variicola, K. quasipneumoniae and K. pneumoniae are closely related bacterial species, misclassification can occur due to mistakes either in normal biochemical tests or during submission to public databases. The objective of this work was to identify K. variicola and K. quasipneumoniae genomes misclassified in GenBank database.

Materials And Methods: Both rpoB phylogenies and average nucleotide identity (ANI) were used to identify a significant number of misclassified Klebsiella spp. genomes.

Results: Here we report an update of K. variicola and K. Quasipneumoniae genomes correctly classified and a list of isolated genomes obtained from humans, plants, animals and insects, described originally as K. pneumoniae or K. variicola, but known now to be misclassified.

Conclusions: This work contributes to recognize the extensive presence of K. variicola and K. quasipneumoniae isolates in diverse sites and samples.
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http://dx.doi.org/10.21149/8149DOI Listing
November 2018

Abundance, diversity and domain architecture variability in prokaryotic DNA-binding transcription factors.

PLoS One 2018 3;13(4):e0195332. Epub 2018 Apr 3.

Laboratorio de Genética Microbiana, Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México, México.

Gene regulation at the transcriptional level is a central process in all organisms, and DNA-binding transcription factors, known as TFs, play a fundamental role. This class of proteins usually binds at specific DNA sequences, activating or repressing gene expression. In general, TFs are composed of two domains: the DNA-binding domain (DBD) and an extra domain, which in this work we have named "companion domain" (CD). This latter could be involved in one or more functions such as ligand binding, protein-protein interactions or even with enzymatic activity. In contrast to DBDs, which have been widely characterized both experimentally and bioinformatically, information on the abundance, distribution, variability and possible role of the CDs is scarce. Here, we investigated these issues associated with the domain architectures of TFs in prokaryotic genomes. To this end, 19 families of TFs in 761 non-redundant bacterial and archaeal genomes were evaluated. In this regard we found four main groups based on the abundance and distribution in the analyzed genomes: i) LysR and TetR/AcrR; ii) AraC/XylS, SinR, and others; iii) Lrp, Fis, ArsR, and others; and iv) a group that included only two families, ArgR and BirA. Based on a classification of the organisms according to the life-styles, a major abundance of regulatory families in free-living organisms, in contrast with pathogenic, extremophilic or intracellular organisms, was identified. Finally, the protein architecture diversity associated to the 19 families considering a weight score for domain promiscuity evidenced which regulatory families were characterized by either a large diversity of CDs, here named as "promiscuous" families given the elevated number of variable domains found in those TFs, or a low diversity of CDs. Altogether this information helped us to understand the diversity and distribution of the 19 Prokaryotes TF families. Moreover, initial steps were taken to comprehend the variability of the extra domain in those TFs, which eventually might assist in evolutionary and functional studies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0195332PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882156PMC
July 2018

Characterization and distribution of GHRH, PACAP, TRH, SST and IGF1 mRNAs in the green iguana.

Gen Comp Endocrinol 2018 01 30;255:90-101. Epub 2017 Sep 30.

Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro, Qro. 76230, Mexico. Electronic address:

The somatotropic axis (SA) regulates numerous aspects of vertebrate physiology such as development, growth, and metabolism and has influence on several tissues including neural, immune, reproductive and gastric tract. Growth hormone (GH) is a key component of SA, it is synthesized and released mainly by pituitary somatotrophs, although now it is known that virtually all tissues can express GH, which, in addition to its well-described endocrine roles, also has autocrine/paracrine/intracrine actions. In the pituitary, GH expression is regulated by several hypothalamic neuropeptides including GHRH, PACAP, TRH and SST. GH, in turn, regulates IGF1 synthesis in several target tissues, adding complexity to the system since GH effects can be exerted either directly or mediated by IGF1. In reptiles, little is known about the SA components and their functional interactions. The aim of this work was to characterize the mRNAs of the principal SA components in the green iguana and to develop the tools that allow the study of the structural and functional evolution of this system in reptiles. By employing RT-PCR and RACE, the cDNAs encoding for GHRH, PACAP, TRH, SST and IGF1 were amplified and sequenced. Results showed that these cDNAs coded for the corresponding protein precursors of 154, 170, 243, 113, and 131 amino acids, respectively. Of these, GHRH, PACAP, SST and IGF1 precursors exhibited a high structural conservation with respect to its counterparts in other vertebrates. On the other hand, iguana's TRH precursor showed 7 functional copies of mature TRH (pyr-QHP-NH), as compared to 4 and 6 copies of TRH in avian and mammalian proTRH sequences, respectively. It was found that in addition to its primary production site (brain for GHRH, PACAP, TRH and SST, and liver for IGF1), they were also expressed in other peripheral tissues, i.e. testes and ovaries expressed all the studied mRNAs, whereas TRH and IGF1 mRNAs were observed ubiquitously in all tissues considered. These results show that the main SA components in reptiles of the Squamata Order maintain a good structural conservation among vertebrate phylogeny, and suggest important physiological interactions (endocrine, autocrine and/or paracrine) between them due to their wide peripheral tissue expression.
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http://dx.doi.org/10.1016/j.ygcen.2017.09.027DOI Listing
January 2018

Dissecting the protein architecture of DNA-binding transcription factors in bacteria and archaea.

Microbiology (Reading) 2017 08 17;163(8):1167-1178. Epub 2017 Aug 17.

Departamento de Ingeniería Celular y Biocatálisis, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México.

Gene regulation at the transcriptional level is a central process in all organisms where DNA-binding transcription factors play a fundamental role. This class of proteins binds specifically at DNA sequences, activating or repressing gene expression as a function of the cell's metabolic status, operator context and ligand-binding status, among other factors, through the DNA-binding domain (DBD). In addition, TFs may contain partner domains (PaDos), which are involved in ligand binding and protein-protein interactions. In this work, we systematically evaluated the distribution, abundance and domain organization of DNA-binding TFs in 799 non-redundant bacterial and archaeal genomes. We found that the distributions of the DBDs and their corresponding PaDos correlated with the size of the genome. We also identified specific combinations between the DBDs and their corresponding PaDos. Within each class of DBDs there are differences in the actual angle formed at the dimerization interface, responding to the presence/absence of ligands and/or crystallization conditions, setting the orientation of the resulting helices and wings facing the DNA. Our results highlight the importance of PaDos as central elements that enhance the diversity of regulatory functions in all bacterial and archaeal organisms, and our results also demonstrate the role of PaDos in sensing diverse signal compounds. The highly specific interactions between DBDs and PaDos observed in this work, together with our structural analysis highlighting the difficulty in predicting both inter-domain geometry and quaternary structure, suggest that these systems appeared once and evolved with diverse duplication events in all the analysed organisms.
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http://dx.doi.org/10.1099/mic.0.000504DOI Listing
August 2017

Tracing the Repertoire of Promiscuous Enzymes along the Metabolic Pathways in Archaeal Organisms.

Life (Basel) 2017 Jul 13;7(3). Epub 2017 Jul 13.

Departamento de Ingeniería Celular y Biocatálisis, Instituto de Biotecnología, Universidad Nacional Autónoma de México, C.P. 62210, Cuernavaca, Morelos, Mexico.

The metabolic pathways that carry out the biochemical transformations sustaining life depend on the efficiency of their associated enzymes. In recent years, it has become clear that promiscuous enzymes have played an important role in the function and evolution of metabolism. In this work we analyze the repertoire of promiscuous enzymes in 89 non-redundant genomes of the Archaea cellular domain. Promiscuous enzymes are defined as those proteins with two or more different Enzyme Commission (E.C.) numbers, according the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. From this analysis, it was found that the fraction of promiscuous enzymes is lower in Archaea than in Bacteria. A greater diversity of superfamily domains is associated with promiscuous enzymes compared to specialized enzymes, both in Archaea and Bacteria, and there is an enrichment of substrate promiscuity rather than catalytic promiscuity in the archaeal enzymes. Finally, the presence of promiscuous enzymes in the metabolic pathways was found to be heterogeneously distributed at the domain level and in the phyla that make up the Archaea. These analyses increase our understanding of promiscuous enzymes and provide additional clues to the evolution of metabolism in Archaea.
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http://dx.doi.org/10.3390/life7030030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617955PMC
July 2017

Towards the complete proteinaceous regulome of .

Microb Genom 2017 03 23;3(3):mgen000107. Epub 2017 Mar 23.

1​Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, 4202 East Fowler Avenue, ISA 2015, Tampa, FL 33620-5150, USA.

The emergence of strains, with broad multidrug-resistance phenotypes and novel virulence factors unique to hypervirulent strains, presents a major threat to human health worldwide. Although a number of studies have described virulence-affecting entities for this organism, very few have identified regulatory elements controlling their expression. Previously, our group has documented the global identification and curation of regulatory RNAs in . As such, in the present study, we detail an extension of this work, the performance of an extensive bioinformatic analysis to identify regulatory proteins in the recently annotated genome of the highly virulent AB5075 strain. In so doing, 243 transcription factors, 14 two-component systems (TCSs), 2 orphan response regulators, 1 hybrid TCS and 5 σ factors were found. A comparison of these elements between AB5075 and other clinical isolates, as well as a laboratory strain, led to the identification of several conserved regulatory elements, whilst at the same time uncovering regulators unique to hypervirulent strains. Lastly, by comparing regulatory elements compiled in this study to genes shown to be essential for AB5075 infection, we were able to highlight elements with a specific importance for pathogenic behaviour. Collectively, our work offers a unique insight into the regulatory network of strains, and provides insight into the evolution of hypervirulent lineages.
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http://dx.doi.org/10.1099/mgen.0.000107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5382811PMC
March 2017

Identification of beta-Lactamases and beta-Lactam-Related Proteins in Human Pathogenic Bacteria using a Computational Search Approach.

Curr Microbiol 2017 Aug 16;74(8):915-920. Epub 2017 May 16.

Departamento de Fisiología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Sierra Mojada #950, colonia Independencia, C.P. 44340, Guadalajara, Jalisco, Mexico.

A systematic analysis of beta-lactamases based on comparative proteomics has not been performed thus far. In this report, we searched for the presence of beta-lactam-related proteins in 591 bacterial proteomes belonging to 52 species that are pathogenic to humans. The amino acid sequences for 19 different types of beta-lactamases (ACT, CARB, CifA, CMY, CTX, FOX, GES, GOB, IMP, IND, KPC, LEN, OKP, OXA, OXY, SHV, TEM, NDM, and VIM) were obtained from the ARG-ANNOT database and were used to construct 19 HMM profiles, which were used to identify potential beta-lactamases in the completely sequenced bacterial proteomes. A total of 2877 matches that included the word "beta-lactamase" and/or "penicillin" in the functional annotation and/or in any of its regions were obtained. These enzymes were mainly described as "penicillin-binding proteins," "beta-lactamases," and "metallo-beta-lactamases" and were observed in 47 of the 52 species studied. In addition, proteins classified as "beta-lactamases" were observed in 39 of the species included. A positive correlation between the number of beta-lactam-related proteins per species and the proteome size was observed (R 0.78, P < 0.00001). This correlation partially explains the high presence of beta-lactam-related proteins in large proteomes, such as Nocardia brasiliensis, Bacillus anthracis, and Mycobacterium tuberculosis, along with their absence in small proteomes, such as Chlamydia spp. and Mycoplasma spp. We detected only five types of beta-lactamases (TEM, SHV, CTX, IMP, and OXA) and other related proteins in particular species that corresponded with those reported in the literature. We additionally detected other potential species-specific beta-lactamases that have not yet been reported. In the future, better results will be achieved due to more accurate sequence annotations and a greater number of sequenced genomes.
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http://dx.doi.org/10.1007/s00284-017-1265-3DOI Listing
August 2017

Identification of DNA Methyltransferase Genes in Human Pathogenic Bacteria by Comparative Genomics.

Indian J Microbiol 2016 Jun 31;56(2):134-41. Epub 2015 Dec 31.

Departamento de Ingeniería de Sistemas Computacionales y Automatización, Instituto de Investigación en Matemáticas Aplicadas y Sistemas (IIMAS), Universidad Nacional Autónoma de México (UNAM), Escolar #300, 04510 Ciudad Universitaria, Distrito Federal Mexico.

DNA methylation plays an important role in gene expression and virulence in some pathogenic bacteria. In this report, we describe DNA methyltransferases (MTases) present in human pathogenic bacteria and compared them with related species, which are not pathogenic or less pathogenic, based in comparative genomics. We performed a search in the KEGG database of the KEGG database orthology groups associated with adenine and cytosine DNA MTase activities (EC: 2.1.1.37, EC: 2.1.1.113 and EC: 2.1.1.72) in 37 human pathogenic species and 18 non/less pathogenic relatives and performed comparisons of the number of these MTases sequences according to their genome size, the DNA MTase type and with their non-less pathogenic relatives. We observed that Helicobacter pylori and Neisseria spp. presented the highest number of MTases while ten different species did not present a predicted DNA MTase. We also detected a significant increase of adenine MTases over cytosine MTases (2.19 vs. 1.06, respectively, p < 0.001). Adenine MTases were the only MTases associated with restriction modification systems and DNA MTases associated with type I restriction modification systems were more numerous than those associated with type III restriction modification systems (0.84 vs. 0.17, p < 0.001); additionally, there was no correlation with the genome size and the total number of DNA MTases, indicating that the number of DNA MTases is related to the particular evolution and lifestyle of specific species, regulating the expression of virulence genes in some pathogenic bacteria.
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http://dx.doi.org/10.1007/s12088-015-0562-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4984436PMC
June 2016

Identification and in silico characterization of two novel genes encoding peptidases S8 found by functional screening in a metagenomic library of Yucatán underground water.

Gene 2016 Nov 10;593(1):154-161. Epub 2016 Aug 10.

Unidad de Biotecnología, Centro de Investigación Científica de Yucatán A.C., Calle 43 No. 130, Chuburná de Hidalgo, Mérida, Yucatán CP 97200, Mexico. Electronic address:

Metagenomics is a culture-independent technology that allows access to novel and potentially useful genetic resources from a wide range of unknown microorganisms. In this study, a fosmid metagenomic library of tropical underground water was constructed, and clones were functionally screened for extracellular proteolytic activity. One of the positive clones, containing a 41,614-bp insert, had two genes with 60% and 68% identity respectively with a peptidase S8 of Chitinimonas koreensis. When these genes were individually sub-cloned, in both cases their sub-clones showed proteolytic phenotype, confirming that they both encode functional proteases. These genes -named PrAY5 and PrAY6- are next to each other. They are similar in size (1845bp and 1824bp respectively) and share 66.5% identity. An extensive in silico characterization showed that their ORFs encode complex zymogens having a signal peptide at their 5' end, followed by a pro-peptide, a catalytic region, and a PPC domain at their 3' end. Their translated sequences were classified as peptidases S8A by sequence comparisons against the non-redundant database and corroborated by Pfam and MEROPS. Phylogenetic analysis of the catalytic region showed that they encode novel proteases that clustered with the sub-family S8_13, which according to the CDD database at NCBI, is an uncharacterized subfamily. They clustered in a clade different from the other three proteases S8 found so far by functional metagenomics, and also different from proteases S8 found in sequenced environmental samples, thereby expanding the range of potentially useful proteases that have been identified by metagenomics. I-TASSER modeling corroborated that they may be subtilases, thus possibly they participate in the hydrolysis of proteins with broad specificity for peptide bonds, and have a preference for a large uncharged residue in P1.
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http://dx.doi.org/10.1016/j.gene.2016.08.009DOI Listing
November 2016

Transcriptomic analysis of the process of biofilm formation in Rhizobium etli CFN42.

Arch Microbiol 2016 Nov 25;198(9):847-60. Epub 2016 May 25.

Programa de Genómica Funcional de Procariotes, Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Apartado Postal 565-A, Cuernavaca, Morelos, Mexico.

Organisms belonging to the genus Rhizobium colonize leguminous plant roots and establish a mutually beneficial symbiosis. Biofilms are structured ecosystems in which microbes are embedded in a matrix of extracellular polymeric substances, and their development is a multistep process. The biofilm formation processes of R. etli CFN42 were analyzed at an early (24-h incubation) and mature stage (72 h), comparing cells in the biofilm with cells remaining in the planktonic stage. A genome-wide microarray analysis identified 498 differentially regulated genes, implying that expression of ~8.3 % of the total R. etli gene content was altered during biofilm formation. In biofilms-attached cells, genes encoding proteins with diverse functions were overexpressed including genes involved in membrane synthesis, transport and chemotaxis, repression of flagellin synthesis, as well as surface components (particularly exopolysaccharides and lipopolysaccharides), in combination with the presence of activators or stimulators of N-acyl-homoserine lactone synthesis This suggests that R. etli is able to sense surrounding environmental conditions and accordingly regulate the transition from planktonic and biofilm growth. In contrast, planktonic cells differentially expressed genes associated with transport, motility (flagellar and twitching) and inhibition of exopolysaccharide synthesis. To our knowledge, this is the first report of nodulation and nitrogen assimilation-related genes being involved in biofilm formation in R. etli. These results contribute to the understanding of the physiological changes involved in biofilm formation by bacteria.
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http://dx.doi.org/10.1007/s00203-016-1241-5DOI Listing
November 2016

The alignment of enzymatic steps reveals similar metabolic pathways and probable recruitment events in Gammaproteobacteria.

BMC Genomics 2015 Nov 17;16:957. Epub 2015 Nov 17.

Departamento de Microbiología Molecular, Instituto de Biotecnología, UNAM, Av. Universidad 2001, Cuernavaca, Morelos, CP 62210, México.

Background: It is generally accepted that gene duplication followed by functional divergence is one of the main sources of metabolic diversity. In this regard, there is an increasing interest in the development of methods that allow the systematic identification of these evolutionary events in metabolism. Here, we used a method not based on biomolecular sequence analysis to compare and identify common and variable routes in the metabolism of 40 Gammaproteobacteria species.

Method: The metabolic maps deposited in the KEGG database were transformed into linear Enzymatic Step Sequences (ESS) by using the breadth-first search algorithm. These ESS represent subsequent enzymes linked to each other, where their catalytic activities are encoded in the Enzyme Commission numbers. The ESS were compared in an all-against-all (pairwise comparisons) approach by using a dynamic programming algorithm, leaving only a set of significant pairs.

Results And Conclusion: From these comparisons, we identified a set of functionally conserved enzymatic steps in different metabolic maps, in which cell wall components and fatty acid and lysine biosynthesis were included. In addition, we found that pathways associated with biosynthesis share a higher proportion of similar ESS than degradation pathways and secondary metabolism pathways. Also, maps associated with the metabolism of similar compounds contain a high proportion of similar ESS, such as those maps from nucleotide metabolism pathways, in particular the inosine monophosphate pathway. Furthermore, diverse ESS associated with the low part of the glycolysis pathway were identified as functionally similar to multiple metabolic pathways. In summary, our comparisons may help to identify similar reactions in different metabolic pathways and could reinforce the patchwork model in the evolution of metabolism in Gammaproteobacteria.
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http://dx.doi.org/10.1186/s12864-015-2113-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4647829PMC
November 2015

RegulonDB version 9.0: high-level integration of gene regulation, coexpression, motif clustering and beyond.

Nucleic Acids Res 2016 Jan 2;44(D1):D133-43. Epub 2015 Nov 2.

Programa de Genómica Computacional, Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, A.P. 565-A, Cuernavaca, Morelos 62100, Mexico

RegulonDB (http://regulondb.ccg.unam.mx) is one of the most useful and important resources on bacterial gene regulation,as it integrates the scattered scientific knowledge of the best-characterized organism, Escherichia coli K-12, in a database that organizes large amounts of data. Its electronic format enables researchers to compare their results with the legacy of previous knowledge and supports bioinformatics tools and model building. Here, we summarize our progress with RegulonDB since our last Nucleic Acids Research publication describing RegulonDB, in 2013. In addition to maintaining curation up-to-date, we report a collection of 232 interactions with small RNAs affecting 192 genes, and the complete repertoire of 189 Elementary Genetic Sensory-Response units (GENSOR units), integrating the signal, regulatory interactions, and metabolic pathways they govern. These additions represent major progress to a higher level of understanding of regulated processes. We have updated the computationally predicted transcription factors, which total 304 (184 with experimental evidence and 120 from computational predictions); we updated our position-weight matrices and have included tools for clustering them in evolutionary families. We describe our semiautomatic strategy to accelerate curation, including datasets from high-throughput experiments, a novel coexpression distance to search for 'neighborhood' genes to known operons and regulons, and computational developments.
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http://dx.doi.org/10.1093/nar/gkv1156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702833PMC
January 2016

Distribution of putative xenogeneic silencers in prokaryote genomes.

Comput Biol Chem 2015 Oct 23;58:167-72. Epub 2015 Jul 23.

Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prol. de Carpio y Plan de Ayala. Col. Sto. Tomás, Distrito Federal, CP 11340, Mexico. Electronic address:

Gene silencing is an important function as it keeps newly acquired foreign DNA repressed, thereby avoiding possible deleterious effects in the host organism. Known transcriptional regulators associated with this process are called xenogeneic silencers (XS) and belong to either the H-NS, Lsr2, MvaT or Rok families. In the work described here we looked for XS-like regulators and their distribution in prokaryotic organisms was evaluated. Our analysis showed that putative XS regulators similar to H-NS, Lsr2, MvaT or Rok are present only in bacteria (31.7%). This does not exclude the existence of alternative XS in the rest of the organisms analyzed. Additionally, of the four XS groups evaluated in this work, those from the H-NS family have diversified more than the other groups. In order to compare the distribution of these putative XS regulators we also searched for other nucleoid-associated proteins (NAPs) not included in this group such as Fis, EbfC/YbaB, HU/IHF and Alba. Results showed that NAPs from the Fis, EbfC/YbaB, HU/IHF and Alba families are widely (94%) distributed among prokaryotes. These NAPs were found in multiple combinations with or without XS-like proteins. In regard with XS regulators, results showed that only XS proteins from one family were found in those organisms containing them. This suggests specificity for this type of regulators and their corresponding genomes.
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http://dx.doi.org/10.1016/j.compbiolchem.2015.06.007DOI Listing
October 2015

The lifestyle of prokaryotic organisms influences the repertoire of promiscuous enzymes.

Proteins 2015 Sep 21;83(9):1625-31. Epub 2015 Jul 21.

Departamento de Ingeniería Celular y Biocatálisis, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México.

The metabolism of microbial organisms and its diversity are partly the result of an adaptation process to the characteristics of the environments that they inhabit. In this work, we analyze the influence of lifestyle on the content of promiscuous enzymes in 761 nonredundant bacterial and archaeal genomes. Promiscuous enzymes were defined as those proteins whose catalytic activities are defined by two or more different Enzyme Commission (E.C.) numbers. The genomes analyzed were categorized into four lifestyles for their exhaustive comparisons: free-living, extremophiles, pathogens, and intracellular. From these analyses we found that free-living organisms have larger genomes and an enrichment of promiscuous enzymes. In contrast, intracellular organisms showed smaller genomes and the lesser proportion of promiscuous enzymes. On the basis of our data, we show that the proportion of promiscuous enzymes in an organism is mainly influenced by the lifestyle, where fluctuating environments promote its emergence. Finally, we evidenced that duplication processes occur preferentially in metabolism of free-living and extremophiles species.
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http://dx.doi.org/10.1002/prot.24847DOI Listing
September 2015

The functional landscape bound to the transcription factors of Escherichia coli K-12.

Comput Biol Chem 2015 Oct 6;58:93-103. Epub 2015 Jun 6.

Department of Biology, Wilfrid Laurier University, 75 University Ave. W., Waterloo, ON N2L 3C5, Canada. Electronic address:

Motivated by the experimental evidences accumulated in the last ten years and based on information deposited in RegulonDB, literature look up, and sequence analysis, we analyze the repertoire of 304 DNA-binding Transcription factors (TFs) in Escherichia coli K-12. These regulators were grouped in 78 evolutionary families and are regulating almost half of the total genes in this bacterium. In structural terms, 60% of TFs are composed by two-domains, 30% are monodomain, and 10% three- and four-structural domains. As previously noticed, the most abundant DNA-binding domain corresponds to the winged helix-turn-helix, with few alternative DNA-binding structures, resembling the hypothesis of successful protein structures with the emergence of new ones at low scales. In summary, we identified and described the characteristics associated to the DNA-binding TF in E. coli K-12. We also identified twelve functional modules based on a co-regulated gene matrix. Finally, diverse regulons were predicted based on direct associations between the TFs and potential regulated genes. This analysis should increase our knowledge about the gene regulation in the bacterium E. coli K-12, and provide more additional clues for comprehensive modelling of transcriptional regulatory networks in other bacteria.
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http://dx.doi.org/10.1016/j.compbiolchem.2015.06.002DOI Listing
October 2015

Comparison of Metabolic Pathways in Escherichia coli by Using Genetic Algorithms.

Comput Struct Biotechnol J 2015 9;13:277-85. Epub 2015 Apr 9.

Departamento de Ingeniería de Sistemas Computacionales y Automatización, IIMAS, Universidad Nacional Autónoma de México, Mexico.

In order to understand how cellular metabolism has taken its modern form, the conservation and variations between metabolic pathways were evaluated by using a genetic algorithm (GA). The GA approach considered information on the complete metabolism of the bacterium Escherichia coli K-12, as deposited in the KEGG database, and the enzymes belonging to a particular pathway were transformed into enzymatic step sequences by using the breadth-first search algorithm. These sequences represent contiguous enzymes linked to each other, based on their catalytic activities as they are encoded in the Enzyme Commission numbers. In a posterior step, these sequences were compared using a GA in an all-against-all (pairwise comparisons) approach. Individual reactions were chosen based on their measure of fitness to act as parents of offspring, which constitute the new generation. The sequences compared were used to construct a similarity matrix (of fitness values) that was then considered to be clustered by using a k-medoids algorithm. A total of 34 clusters of conserved reactions were obtained, and their sequences were finally aligned with a multiple-sequence alignment GA optimized to align all the reaction sequences included in each group or cluster. From these comparisons, maps associated with the metabolism of similar compounds also contained similar enzymatic step sequences, reinforcing the Patchwork Model for the evolution of metabolism in E. coli K-12, an observation that can be expanded to other organisms, for which there is metabolism information. Finally, our mapping of these reactions is discussed, with illustrations from a particular case.
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http://dx.doi.org/10.1016/j.csbj.2015.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4423528PMC
May 2015