Comparative genome mining and heterologous expression of an orphan NRPS gene cluster direct the production of ashimides
作者： Jing Shi , Ying Jie Zeng , Bo Zhang , Fen Li Shao , Yan Chi Chen
DOI: 10.1039/C8SC05670F
关键词: Computational biology 、 Gene cluster 、 Gene 、 Genome 、 Biosynthesis 、 Heterologous expression 、 Natural product 、 Biology 、 Streptomyces 、 Nonribosomal peptide
摘要: The ever-increasing bacterial genomic repositories reveal a great number of uncharacterized biosynthetic gene clusters, representing tremendous resource for natural product discovery. Genome mining the marine Streptomyces sp. NA03103 indicates presence an orphan nonribosomal peptide synthetase (NRPS) cluster (asm), to which there are no homologous clusters in public genome databases. Heterologous expression asm S. lividans SBT18 strain led discovery two novel cyclopeptides, ashimides A and B (1 2), with 2 showing cytotoxic activity. In addition, we use bioinformatic analysis, inactivation stable isotope labelling experiments, as well vitro biochemical assays, present coherent assembly line ashimide biosynthesis, featuring unusual desaturation, halogenation cyclization cascade catalyzed by P450 monooxygenase FAD-dependent halogenase.
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