Premium
Characterization of a Single Gene Cluster Responsible for Methylpendolmycin and Pendolmycin Biosynthesis in the Deep Sea Bacterium Marinactinospora thermotolerans
Author(s) -
Ma Junying,
Zuo Dianguang,
Song Yongxiang,
Wang Bo,
Huang Hongbo,
Yao Yueliang,
Li Wenjun,
Zhang Si,
Zhang Changsheng,
Ju Jianhua
Publication year - 2012
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201100700
Subject(s) - prenyltransferase , gene cluster , biosynthesis , nonribosomal peptide , biochemistry , prenylation , gene , cytochrome p450 , natural product , biology , bacteria , enzyme , chemistry , genetics
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.