Characterization of a Single Gene Cluster Responsible for Methylpendolmycin and Pendolmycin Biosynthesis in the Deep Sea Bacterium Marinactinospora thermotolerans

• Published in: Chembiochem : a European journal of chemical biology Vol. 13; no. 4; pp. 547 - 552
• Main Authors: Ma, Junying, Zuo, Dianguang, Song, Yongxiang, Wang, Bo, Huang, Hongbo, Yao, Yueliang, Li, Wenjun, Zhang, Si, Zhang, Changsheng, Ju, Jianhua
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 05.03.2012; WILEY‐VCH Verlag
• Subjects: Actinomycetales - chemistry; Actinomycetales - metabolism; Alkaloids - biosynthesis; Alkaloids - chemistry; Biocatalysis; biosynthesis; Computational Biology; Cytochrome P-450 Enzyme System - genetics; Cytochrome P-450 Enzyme System - metabolism; Dimethylallyltranstransferase - genetics; Dimethylallyltranstransferase - metabolism; Genetic Engineering; Indoles - chemistry; Lactams - chemistry; methylpendolmycin; Molecular Conformation; Multigene Family - genetics; natural products; pendolmycin; Peptide Synthases - genetics; Peptide Synthases - metabolism; prenyltransferases; Stereoisomerism
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.201100700

The nine‐membered indolactam antibiotics belong to a small group of antibiotics showing broad biological activities. However, the in vivo genetic engineering of compounds of this type has not been performed. Here we report the identification of a single gene cluster responsible for the biosynthesis of methylpendolmycin and pendolmycin, two members of this family of antibiotics, from the deep sea bacterium Marinactinospora thermotolerans SCSIO 00652. Bioinformatics analysis and gene inactivation, coupled with metabolite characterization, reveal that MpnB, a nonribosomal peptide synthetase, MpnC, a cytochrome P450, and MpnD, a prenyltransferase, are sufficient to catalyze the biosynthesis of the two antibiotics from L‐Ile (or L‐Val), L‐Trp, and methionine. MpnD is the first identified enzyme that transfers a C5 prenyl unit in a reverse manner to the C‐7 position of a Trp‐derived natural product. Indolactam alkaloids: A single gene cluster responsible for biosynthesis of methylpendolmycin and pendolmycin has been characterized. Bioinformatics analysis and gene inactivation, coupled with metabolite characterization, reveal that MpnB (a nonribosomal peptide synthetase), MpnC (a cytochrome P450), and MpnD (a prenyltransferase) are sufficient to catalyze the biosynthesis of the two antibiotics from L‐Ile (or L‐Val), L‐Trp, and methionine.