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B6db references: 30996885

type Journal Article
authors Shi J, Zeng YJ, Zhang B, Shao FL, Chen YC, Xu X, Sun Y, Xu Q, Tan RX, Ge HM
title Comparative genome mining and heterologous expression of an orphan NRPS gene cluster direct the production of ashimides
journal Chem Sci
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ui 30996885
year (2019)
volume 10
number 10
pages 3042-3048
keywords doi: 10.1039/c8sc05670f.
abstract The ever-increasing bacterial genomic repositories reveal a great number of uncharacterized biosynthetic gene clusters, representing a tremendous resource for natural product discovery. Genome mining of the marine Streptomyces sp. NA03103 indicates the presence of an orphan nonribosomal peptide synthetase (NRPS) gene cluster (asm), to which there are no homologous gene clusters in the public genome databases. Heterologous expression of the asm gene cluster in the S. lividans SBT18 strain led to the discovery of two novel cyclopeptides, ashimides A and B (1 and 2), with 2 showing cytotoxic activity. In addition, we use bioinformatic analysis, gene inactivation and stable isotope labelling experiments, as well as in vitro biochemical assays, to present a coherent and novel assembly line for ashimide biosynthesis, featuring an unusual desaturation, halogenation and cyclization cascade catalyzed by a P450 monooxygenase and a FAD-dependent halogenase.
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