Divergent Metabolism of Cyclo-l-Trp-l-Leu in Streptomyces albofaciens by Hydroxylation and Nucleobase Transfer with Two Cytochrome P450 Enzymes.

IF 3.3 2区生物学 Q2 CHEMISTRY, MEDICINAL

Journal of Natural Products Pub Date : 2024-12-09 DOI:10.1021/acs.jnatprod.4c00837

Yu Dai, Daniel Ostendorff, Shu-Ming Li

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引用次数: 0

Abstract

A three-gene salb cluster from Streptomyces albofaciens was proven to be responsible for the formation of cyclo-l-Trp-l-Leu (cWL) derivatives. An Escherichia coli strain harboring the cyclodipeptide synthase (CDPS) gene salbA produced cWL. Expression of the whole cluster or genes of various combinations in Streptomyces coelicolor revealed different metabolites of cWL by two cytochrome P450 enzymes. Isolation and structure elucidation proved the conversion of cWL to guatrypleumycine A by nucleobase transfer with SalbB and to cyclo(trans-10-hydroxy-l-Trp-l-Leu) by hydroxylation with SalbC. Incubation with ¹⁵NH₄Cl supported the incorporation of guanine in guatrypleumycine A and an X-ray crystallographic study confirmed the stereospecific hydroxylation at C-10 of the tryptophanyl residue. Cultivation of the salbB or salbC expression strains with different substrates further proved the divergent metabolisms of cWL. To the best of our knowledge, SalbC is the first report of the P450 enzyme from CDPS-associated pathways to catalyze β-hydroxylation at the amino acid side chain.

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来源期刊

Journal of Natural Products 生物-药学

CiteScore

9.10

自引率

5.90%

发文量

294

审稿时长

2.3 months

期刊介绍： The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin. When new compounds are reported, manuscripts describing their biological activity are much preferred. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.