title: Characterization of a single gene cluster responsible for methylpendolmycin and pendolmycin biosynthesis in the deep sea bacterium Marinactinospora thermotolerans.
abstract: 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.
authors.affiliation: Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China.
authors.forename: Junying
authors.initials: J
authors.lastname: Ma
authors.forename: Dianguang
authors.initials: D
authors.lastname: Zuo
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Song
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.forename: Hongbo
authors.initials: H
authors.lastname: Huang
authors.forename: Yueliang
authors.initials: Y
authors.lastname: Yao
authors.forename: Wenjun
authors.initials: W
authors.lastname: Li
authors.forename: Si
authors.initials: S
authors.lastname: Zhang
authors.forename: Changsheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Ju
mesh_terms: D000192:Actinomycetales / Q000737:chemistry / Q000378:metabolism*; D000470:Alkaloids / Q000096:biosynthesis* / Q000737:chemistry; D055162:Biocatalysis; D019295:Computational Biology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004122:Dimethylallyltranstransferase / Q000235:genetics* / Q000378:metabolism*; D005818:Genetic Engineering; D007211:Indoles / Q000737:chemistry; D007769:Lactams / Q000737:chemistry; D008968:Molecular Conformation; D005810:Multigene Family / Q000235:genetics; D010453:Peptide Synthases / Q000235:genetics* / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; D007211:Indoles; D007769:Lactams; C059313:pendolmycin; C073640:methylpendolmycin; D003577:Cytochrome P-450 Enzyme System; D004122:Dimethylallyltranstransferase; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase