4,054 results match your criteria prenylation


Cholesterol synthesis inhibition or depletion in axon regeneration.

Authors:
Bor Luen Tang

Neural Regen Res 2022 Feb;17(2):271-276

Department of Biochemistry, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore.

Cholesterol is biosynthesized by all animal cells. Beyond its metabolic role in steroidogenesis, it is enriched in the plasma membrane where it has key structural and regulatory functions. Cholesterol is thus presumably important for post-injury axon regrowth, and this notion is supported by studies showing that impairment of local cholesterol reutilization impeded regeneration. Read More

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February 2022

Mevalonate blockade in cancer cells triggers CLEC9A+ dendritic cell-mediated antitumor immunity.

Cancer Res 2021 Jul 15. Epub 2021 Jul 15.

Experiment Medicine, Sun Yat-sen University Cancer Center

Hyperactive mevalonate (MVA) metabolic activity is often observed in cancer cells, and blockade of this pathway inhibits tumor cell lipid synthesis and cell growth and enhances tumor immunogenicity. How tumor cell MVA metabolic blockade promotes antitumor immune responses, however, remains unclear. Here we show that inhibition of the MVA metabolic pathway in tumor cells elicits type 1 classical dendritic cells (cDC1)-mediated tumor recognition and antigen cross-presentation for antitumor immunity. Read More

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Expression of Rab Prenylation Pathway Genes and Relation to Disease Progression in Choroideremia.

Transl Vis Sci Technol 2021 Jul;10(8):12

Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.

Purpose: Choroideremia results from the deficiency of Rab Escort Protein 1 (REP1), encoded by CHM, involved in the prenylation of Rab GTPases. Here, we investigate whether the transcription and expression of other genes involved in the prenylation of Rab proteins correlates with disease progression in a cohort of patients with choroideremia.

Methods: Rates of retinal pigment epithelial area loss in 41 patients with choroideremia were measured using fundus autofluorescence imaging for up to 4 years. Read More

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Targeting Small GTPases and Their Prenylation in Diabetes Mellitus.

J Med Chem 2021 Jul 8;64(14):9677-9710. Epub 2021 Jul 8.

Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, Żeromskiego Street 116, 90-924 Łódź, Poland.

A fundamental role of pancreatic β-cells to maintain proper blood glucose level is controlled by the Ras superfamily of small GTPases that undergo post-translational modifications, including prenylation. This covalent attachment with either a farnesyl or a geranylgeranyl group controls their localization, activity, and protein-protein interactions. Small GTPases are critical in maintaining glucose homeostasis acting in the pancreas and metabolically active tissues such as skeletal muscles, liver, or adipocytes. Read More

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SmgGDS: An Emerging Master Regulator of Prenylation and Trafficking by Small GTPases in the Ras and Rho Families.

Front Mol Biosci 2021 16;8:685135. Epub 2021 Jun 16.

Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, United States.

Newly synthesized small GTPases in the Ras and Rho families are prenylated by cytosolic prenyltransferases and then escorted by chaperones to membranes, the nucleus, and other sites where the GTPases participate in a variety of signaling cascades. Understanding how prenylation and trafficking are regulated will help define new therapeutic strategies for cancer and other disorders involving abnormal signaling by these small GTPases. A growing body of evidence indicates that splice variants of SmgGDS (gene name RAP1GDS1) are major regulators of the prenylation, post-prenylation processing, and trafficking of Ras and Rho family members. Read More

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Metabolome analysis revealed that soybean-Aspergillus oryzae interaction induced dynamic metabolic and daidzein prenylation changes.

PLoS One 2021 2;16(7):e0254190. Epub 2021 Jul 2.

Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.

Several isoflavonoids are well known for their ability to act as soybean phytoalexins. However, the overall effects of the soybean-Aspergillus oryzae interaction on metabolism remain largely unknown. The aim of this study is to reveal an overview of nutritive and metabolic changes in germinated and A. Read More

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Protein Prenylation and Hsp40 in Thermotolerance of Plasmodium falciparum Malaria Parasites.

mBio 2021 06 29;12(3):e0076021. Epub 2021 Jun 29.

Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.

During its complex life cycle, the malaria parasite survives dramatic environmental stresses, including large temperature shifts. Protein prenylation is required during asexual replication of Plasmodium falciparum, and the canonical heat shock protein 40 protein (HSP40; PF3D7_1437900) is posttranslationally modified with a 15-carbon farnesyl isoprenyl group. In other organisms, farnesylation of Hsp40 orthologs controls their localization and function in resisting environmental stress. Read More

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Argicyclamides A-C Unveil Enzymatic Basis for Guanidine Bis-prenylation.

J Am Chem Soc 2021 Jul 28;143(27):10083-10087. Epub 2021 Jun 28.

Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.

Guanidine prenylation is an outstanding modification in alkaloid and peptide biosynthesis, but its enzymatic basis has remained elusive. We report the isolation of argicyclamides, a new class of cyanobactins with unique mono- and bis-prenylations on guanidine moieties, from NIES-88. The genetic basis of argicyclamide biosynthesis was established by the heterologous expression and characterization of biosynthetic enzymes including AgcF, a new guanidine prenyltransferase. Read More

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Gene Encodes a Flavonoid Prenyltransferase in White Lupin.

Front Plant Sci 2021 11;12:673337. Epub 2021 Jun 11.

Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.

Legume plants are rich in prenylated flavonoid compounds, which play an important role in plant defense and human health. In the present study, we identified a prenyltransferase (PT) gene, named , in white lupin (), which shows a high identity and close relationship with the other known PT genes involved in flavonoid prenylation in planta. The recombinant LaPT2 protein expressed in yeast cells exhibited a relatively strong activity toward several flavonols (e. Read More

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Photoredox catalysis on unactivated substrates with strongly reducing iridium photosensitizers.

Chem Sci 2021 Jan 29;12(11):4069-4078. Epub 2021 Jan 29.

Department of Chemistry, University of Houston 3585 Cullen Blvd., Room 112 Houston TX 77204-5003 USA

Photoredox catalysis has emerged as a powerful strategy in synthetic organic chemistry, but substrates that are difficult to reduce either require complex reaction conditions or are not amenable at all to photoredox transformations. In this work, we show that strong bis-cyclometalated iridium photoreductants with electron-rich β-diketiminate (NacNac) ancillary ligands enable high-yielding photoredox transformations of challenging substrates with very simple reaction conditions that require only a single sacrificial reagent. Using blue or green visible-light activation we demonstrate a variety of reactions, which include hydrodehalogenation, cyclization, intramolecular radical addition, and prenylation radical-mediated pathways, with optimized conditions that only require the photocatalyst and a sacrificial reductant/hydrogen atom donor. Read More

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January 2021

New therapies for hepatitis delta virus infection.

Liver Int 2021 06;41 Suppl 1:30-37

Centre de recherche sur l'inflammation, Université de Paris, Inserm, CNRS, Paris, France.

Hepatitis delta virus (HDV) infection is a defective virus requiring hepatitis B virus (HBV) for its complete replication cycle. HDV is a small hepatotropic RNA virus and around 15 to 25 million people worldwide are living with chronic hepatitis delta (CHD) infection. However, the prevalence of HDV may be underestimated, and screening is frequently insufficient. Read More

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Cholesterol Metabolic Reprogramming in Cancer and Its Pharmacological Modulation as Therapeutic Strategy.

Front Oncol 2021 24;11:682911. Epub 2021 May 24.

Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.

Cholesterol is a ubiquitous sterol with many biological functions, which are crucial for proper cellular signaling and physiology. Indeed, cholesterol is essential in maintaining membrane physical properties, while its metabolism is involved in bile acid production and steroid hormone biosynthesis. Additionally, isoprenoids metabolites of the mevalonate pathway support protein-prenylation and dolichol, ubiquinone and the heme biosynthesis. Read More

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A short C-terminal peptide in Gγ regulates Gβγ signaling efficacy.

Mol Biol Cell 2021 Jun 9:mbcE20110750. Epub 2021 Jun 9.

Department of Chemistry and Biochemistry, The University of Toledo, Toledo, OH 43606, USA.

G protein beta-gamma (Gβγ) subunits anchor to the plasma membrane (PM) through the carboxy-terminal (CT) prenyl group in Gγ. This interaction is crucial for the PM localization and functioning of Gβγ, allowing GPCR-G protein signaling to proceed. The diverse Gγ family has twelve members, and we have recently shown that the signaling efficacies of major Gβγ effectors are Gγ-type dependent. Read More

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Hepatitis D virus in 2021: virology, immunology and new treatment approaches for a difficult-to-treat disease.

Gut 2021 Jun 8. Epub 2021 Jun 8.

Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Approximately 5% of individuals infected with hepatitis B virus (HBV) are coinfected with hepatitis D virus (HDV). Chronic HBV/HDV coinfection is associated with an unfavourable outcome, with many patients developing liver cirrhosis, liver failure and eventually hepatocellular carcinoma within 5-10 years. The identification of the HBV/HDV receptor and the development of novel in vitro and animal infection models allowed a more detailed study of the HDV life cycle in recent years, facilitating the development of specific antiviral drugs. Read More

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The main post-translational modifications and related regulatory pathways in the malaria parasite Plasmodium falciparum: An update.

J Proteomics 2021 Aug 2;245:104279. Epub 2021 Jun 2.

Proteomics Unit, Cancer Research Centre (IBMCC/CSIC/USAL/IBSAL), 37007, Salamanca, Spain. Electronic address:

There are important challenges when investigating individual post-translational modifications (PTMs) or protein interaction network and delineating if PTMs or their changes and cross-talks are involved during infection, disease initiation or as a result of disease progression. Proteomics and in silico approaches now offer the possibility to complement each other to further understand the regulatory involvement of these modifications in parasites and infection biology. Accordingly, the current review highlights key expressed or altered proteins and PTMs are invisible switches that turn on and off the function of most of the proteins. Read More

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Prenylated Flavonoids with Potential Antimicrobial Activity: Synthesis, Biological Activity, and In Silico Study.

Int J Mol Sci 2021 May 22;22(11). Epub 2021 May 22.

Programa Centro de Investigaciones Biomédicas Aplicadas, Escuela de Medicina, Facultad de Ciencias Médicas, Universidad de Santiago de Chile, Santiago 9170022, Chile.

Prenylated flavonoids are an important class of naturally occurring flavonoids with important biological activity, but their low abundance in nature limits their application in medicines. Here, we showed the hemisynthesis and the determination of various biological activities of seven prenylated flavonoids, named , with an emphasis on antimicrobial ones. Compounds , , and showed inhibitory activity against human pathogenic fungi. Read More

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Flavonoids from the Genus Isolation, Structure, Pharmacological Activities and Structure-Activity Relationships.

Pharmaceuticals (Basel) 2021 May 2;14(5). Epub 2021 May 2.

Department of Chemistry, Tshwane University of Technology, Pretoria 0001, South Africa.

Plants of the genus are widely distributed across temperate, tropical and subtropical regions of South America, Asia and Africa with established Ayurvedic, Chinese and Malay ethnomedical records. The present review reports the isolation, occurrence, phytochemistry, biological properties, therapeutic potential and structure-activity relationship of flavonoids for the period covering 2000-2020, while identifying potential areas for future studies aimed at development of new therapeutic agents from these plants. The findings suggest that the extracts and isolated flavonoids possess anticancer, antiproliferative, antimalarial, antibacterial, anti-venom, anti-inflammatory, anti-hepatitis and antioxidant properties and have different mechanisms of action against cancer cells. Read More

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Bioinspired Brønsted Acid-Promoted Regioselective Tryptophan Isoprenylations.

ACS Omega 2021 Apr 12;6(16):10840-10858. Epub 2021 Apr 12.

Departments of Chemistry & Biology, Indian Institute of Science Education and Research, Tirupati 517507, Andhra Pradesh India.

Tryptophan-containing isoprenoid indole alkaloid natural products are well known for their intricate structural architectures and significant biological activities. Nature employs dimethylallyl tryptophan synthases (DMATSs) or aromatic indole prenyltransferases (iPTs) to catalyze regio- and stereoselective prenylation of l-Trp. Regioselective synthetic routes that isoprenylate -Trp-Trp in a 2,5-diketopiperazine (DKP) core, in a desymmetrizing manner, are nonexistent and are highly desirable. Read More

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Plant Natural Flavonoids Against Multidrug Resistant Pathogens.

Adv Sci (Weinh) 2021 May 26:e2100749. Epub 2021 May 26.

National Center for Veterinary Drug Safety Evaluation, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.

The increasing emergence and dissemination of multidrug resistant (MDR) bacterial pathogens accelerate the desires for new antibiotics. Natural products dominate the preferred chemical scaffolds for the discovery of antibacterial agents. Here, the potential of natural flavonoids from plants against MDR bacteria, is demonstrated. Read More

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Timing of geranylgeraniol addition increases osteoblast activities under alendronate condition.

J Oral Biol Craniofac Res 2021 Jul-Sep;11(3):396-401. Epub 2021 May 5.

Thammasat University Research Unit in Dental and Bone Substitute Biomaterials, Faculty of Dentistry, Thammasat University, Pathumthani, Thailand.

Background: Alendronate (ALN), a nitrogen-containing bisphosphonate, is prescribed to treat bone diseases. ALN acts as an inhibitor of enzymes in the mevalonate pathway, which results in reducing osteoblast viability and mineralization. Geranylgeraniol (GGOH) is a substrate in mevalonate pathway and mediates protein prenylation in the cells. Read More

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HSP70-4 and farnesylated AtJ3 constitute a specific HSP70/HSP40-based chaperone machinery essential for prolonged heat stress tolerance in Arabidopsis.

J Plant Physiol 2021 Jun 29;261:153430. Epub 2021 Apr 29.

Department of Life Sciences, National Central University, 300 Jhong-Da Road, Jhong-Li District, Taoyuan City 32001, Taiwan. Electronic address:

AtJ3 (J3)-a member of the Arabidopsis cytosolic HSP40 family-harbors a C-terminal CaaX motif for farnesylation, which is exclusively catalyzed by protein farnesyltransferase (PFT). Previously, prolonged incubation at 37 °C for 4 d was found to be lethal to the heat-intolerant 5 (hit5) mutant lacking PFT and transgenic j3 plants expressing a CaaX-abolishing J3 construct, indicating that farnesylated J3 is essential for heat tolerance in plants. Given the role of HSP40s as cochaperones of HSP70s, the thermal sensitivity of five individual cytosolic HSP70 (HSP70-1 to HSP70-5) knockout mutants was tested in this study. Read More

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Production and Membrane Binding of N-Terminally Acetylated, C-Terminally Farnesylated and Carboxymethylated KRAS4b.

Methods Mol Biol 2021 ;2262:105-116

NCI RAS Initiative, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.

Recombinant mammalian proteins are routinely produced in E. coli and thus lack post-translational modifications. KRAS4b is processed at both the N- and C-terminus, resulting in an acetylation of the N-terminus (at Thr, after aminopeptidase removal of the original N-term Met) and farnesylation/carboxymethylation of the C-terminal Cys (after proteolytic cleavage of the original C-terminal three amino acids, Val-Iso-Met). Read More

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Exploring boron applications in modern agriculture: A structure-activity relationship study of a novel series of multi-substitution benzoxaboroles for identification of potential fungicides.

Bioorg Med Chem Lett 2021 Jul 5;43:128089. Epub 2021 May 5.

Boragen, Inc., 5 Laboratory Drive, Suite 2150, Research Triangle Park, Durham, NC 27709, USA.

Several boron-containing small molecules have been approved by the US FDA to treat human diseases. We explored potential applications of boron-containing compounds in modern agriculture by pursuing multiple research and development programs. Here, we report a novel series of multi-substitution benzoxaboroles (1-36), a compound class that we recently reported as targeting geranylgeranyl transferase I (GGTase I) and thereby inhibiting protein prenylation (Kim et al. Read More

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Exploiting the anticancer effects of a nitrogen bisphosphonate nanomedicine for glioblastoma multiforme.

J Nanobiotechnology 2021 May 4;19(1):127. Epub 2021 May 4.

School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK.

Glioblastoma multiforme (GBM) is an incurable aggressive brain cancer in which current treatment strategies have demonstrated limited survival benefit. In recent years, nitrogen-containing bisphosphonates (N-BPs) have demonstrated direct anticancer effects in a number of tumour types including GBM. In this study, a nano-formulation with the RALA peptide was used to complex the N-BP, alendronate (ALN) into nanoparticles (NPs) < 200 nm for optimal endocytic uptake. Read More

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Farnesylation of Zebrafish G-Protein-Coupled Receptor Kinase Using Bio-orthogonal Labeling.

ACS Chem Neurosci 2021 05 4;12(10):1824-1832. Epub 2021 May 4.

Division of Biochemistry, Department of Neurosciences, Carl von Ossietzky Universität Oldenburg, D-26111 Oldenburg, Germany.

G-protein-coupled receptors are deactivated or desensitized by phosphorylation by respective G-protein-coupled receptor kinases (GRKs). In zebrafish rod and cone photoreceptor cells, four orthologous GRKs are expressed participating in the deactivation of rod and cone opsins. An important feature of GRKs in general is the consensus sites for lipid modification, which would allow the posttranslational attachment of isoprenoids facilitating membrane association and enzymatic performance. Read More

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Statins repress needle-like carbon nanotube- or cholesterol crystal-stimulated IL-1β production by inhibiting the uptake of crystals by macrophages.

Biochem Pharmacol 2021 Jun 28;188:114580. Epub 2021 Apr 28.

National Institute of Health Sciences, Kanagawa 210-9501, Japan. Electronic address:

Statins are 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors that lower atherogenic LDL-cholesterol levels. Statins exert clinically relevant anti-inflammatory effects; however, the underlying molecular mechanism remains unclear. Studies have shown that endogenous and exogenous pathogenic crystals, such as cholesterol and monosodium urate (MSU), and needle-like nanomaterials, such as multi-wall carbon nanotubes (MWCNT), induce the production of IL-1β and play a critical role in the development of crystal-associated sterile inflammatory pathologies. Read More

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Identification of a Prenyl Chalcone as a Competitive Lipoxygenase Inhibitor: Screening, Biochemical Evaluation and Molecular Modeling Studies.

Molecules 2021 Apr 12;26(8). Epub 2021 Apr 12.

Núcleo de Bioensaios, Biossíntese e Ecofisiologia de Produtos Naturais (NuBBE), Departamento de Química Orgânica, Instituto de Química, Universidade Estadual Paulista (UNESP), Araraquara, SP 14800-060, Brazil.

Cyclooxygenase (COX) and lipoxygenase (LOX) are key targets for the development of new anti-inflammatory agents. LOX, which is involved in the biosynthesis of mediators in inflammation and allergic reactions, was selected for a biochemical screening campaign to identify LOX inhibitors by employing the main natural product library of Brazilian biodiversity. Two prenyl chalcones were identified as potent inhibitors of LOX-1 in the screening. Read More

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Parallel evolution of UbiA superfamily proteins into aromatic -prenyltransferases in plants.

Proc Natl Acad Sci U S A 2021 Apr;118(17)

Laboratory of Plant Gene Expression, Research Institute for Sustainable Humanosphere, Kyoto University, Uji 611-0011, Japan;

Plants produce ∼300 aromatic compounds enzymatically linked to prenyl side chains via C-O bonds. These -prenylated aromatic compounds have been found in taxonomically distant plant taxa, with some of them being beneficial or detrimental to human health. Although their -prenyl moieties often play crucial roles in the biological activities of these compounds, no plant gene encoding an aromatic -prenyltransferase (-PT) has been isolated to date. Read More

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A versatile cis-prenyltransferase from Methanosarcina mazei catalyzes both C- and O-prenylations.

J Biol Chem 2021 Jan-Jun;296:100679. Epub 2021 Apr 17.

Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi, Japan. Electronic address:

Polyprenyl groups, products of isoprenoid metabolism, are utilized in peptidoglycan biosynthesis, protein N-glycosylation, and other processes. These groups are formed by cis-prenyltransferases, which use allylic prenyl pyrophosphates as prenyl-donors to catalyze the C-prenylation of the general acceptor substrate, isopentenyl pyrophosphate. Repetition of this reaction forms (Z,E-mixed)-polyprenyl pyrophosphates, which are converted later into glycosyl carrier lipids, such as undecaprenyl phosphate and dolichyl phosphate. Read More

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Synthetic production of prenylated naringenins in yeast using promiscuous microbial prenyltransferases.

Metab Eng Commun 2021 Jun 19;12:e00169. Epub 2021 Mar 19.

Graduate School of Science, Technology and Innovation, Kobe University, 1-1 Rokkodai, Nada, Kobe, 657-8501, Japan.

Reconstitution of prenylflavonoids using the flavonoid biosynthetic pathway and prenyltransferases (PTs) in microbes can be a promising attractive alternative to plant-based production or chemical synthesis. Here, we demonstrate that promiscuous microbial PTs can be a substitute for regiospecific but mostly unidentified botanical PTs. To test the prenylations of naringenin, we constructed a yeast strain capable of producing naringenin from l-phenylalanine by genomic integration of six exogenous genes encoding components of the naringenin biosynthetic pathway. Read More

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