BMC Evol Biol 2015 Jun 10;15:107. Epub 2015 Jun 10.
Evolution of Metabolic Diversity, Unidad de Genómica Avanzada (Langebio), Cinvestav-IPN, Km 9.6 Libramiento Norte, Carretera Irapuato - León, CP 36821, Irapuato, México.
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Biochem J 2016 05 29;473(9):1141-52. Epub 2016 Feb 29.
Evolution of Metabolic Diversity Laboratory, Unidad de Genómica Avanzada (Langebio), Cinvestav-IPN, Irapuato, CP36821, México
We investigate the evolution of co-occurring analogous enzymes involved in L-tryptophan and L-histidine biosynthesis in Actinobacteria Phylogenetic analysis of trpF homologues, a missing gene in certain clades of this lineage whose absence is complemented by a dual-substrate HisA homologue, termed PriA, found that they fall into three categories: (i) trpF-1, an L-tryptophan biosynthetic gene horizontally acquired by certain Corynebacterium species; (ii) trpF-2, a paralogue known to be involved in synthesizing a pyrrolopyrrole moiety and (iii) trpF-3, a variable non-conserved orthologue of trpF-1 We previously investigated the effect of trpF-1 upon the evolution of PriA substrate specificity, but nothing is known about the relationship between trpF-3 and priA After in vitro steady-state enzyme kinetics we found that trpF-3 encodes a phosphoribosyl anthranilate isomerase. However, mutation of this gene in Streptomyces sviceus did not lead to auxothrophy, as expected from the biosynthetic role of trpF-1 Biochemical characterization of a dozen co-occurring TrpF-2 or TrpF-3, with PriA homologues, explained the prototrophic phenotype, and unveiled an enzyme activity trade-off between TrpF and PriA. X-ray structural analysis suggests that the function of these PriA homologues is mediated by non-conserved mutations in the flexible L5 loop, which may be responsible for different substrate affinities. Read More
PLoS Genet 2016 Jan 29;12(1):e1005836. Epub 2016 Jan 29.
Institute of Biophysics and Physical Biochemistry, University of Regensburg, Regensburg, Germany.
Modern enzymes are highly optimized biocatalysts that process their substrates with extreme efficiency. Many enzymes catalyze more than one reaction; however, the persistence of such ambiguities, their consequences and evolutionary causes are largely unknown. As a paradigmatic case, we study the history of bi-functionality for a time span of approximately two billion years for the sugar isomerase HisA from histidine biosynthesis. Read More
Proc Natl Acad Sci U S A 2011 Mar 14;108(9):3554-9. Epub 2011 Feb 14.
European Molecular Biology Laboratory, Hamburg Unit, Notkestrasse 85, D-22603 Hamburg, Germany.
In histidine and tryptophan biosynthesis, two related isomerization reactions are generally catalyzed by two specific single-substrate enzymes (HisA and TrpF), sharing a similar (β/α)(8)-barrel scaffold. However, in some actinobacteria, one of the two encoding genes (trpF) is missing and the two reactions are instead catalyzed by one bisubstrate enzyme (PriA). To unravel the unknown mechanism of bisubstrate specificity, we used the Mycobacterium tuberculosis PriA enzyme as a model. Read More
Mol Biol Evol 2013 Sep 25;30(9):2024-34. Epub 2013 Jun 25.
Evolution of Metabolic Diversity Laboratory, Laboratorio Nacional de Genómica para la Biodiversidad (Langebio), Cinvestav-IPN, Irapuato, México.
Despite the prominent role of horizontal gene transfer (HGT) in shaping bacterial metabolism, little is known about the impact of HGT on the evolution of enzyme function. Specifically, what is the influence of a recently acquired gene on the function of an existing gene? For example, certain members of the genus Corynebacterium have horizontally acquired a whole l-tryptophan biosynthetic operon, whereas in certain closely related actinobacteria, for example, Mycobacterium, the trpF gene is missing. In Mycobacterium, the function of the trpF gene is performed by a dual-substrate (βα)8 phosphoribosyl isomerase (priA gene) also involved in l-histidine (hisA gene) biosynthesis. Read More