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Title: Characterization of the biosynthetic gene cluster for maklamicin, a spirotetronate-class antibiotic of the endophytic Micromonospora sp. NBRC 110955
Authors: Ratama Daduang
Shigeru Kitani
Junko Hashimoto
Arinthip Thamchaipenet
Yasuhiro Igarashi
Kazuo Shin-ya
Haruo Ikeda
Takuya Nihira
Osaka University
Japan Biological Informatics Consortium (JBIC)
Kasetsart University
Toyama Prefectural University
Kitasato University
Mahidol University
Keywords: Immunology and Microbiology
Issue Date: 1-Jan-2015
Citation: Microbiological Research. Vol.180, (2015), 30-39
Abstract: © 2015 Elsevier GmbH. Maklamicin, which is produced by the endophytic Micromonospora sp. NBRC 110955, is a spirotetronate-class antibiotic possessing anti-microbial activity against Gram-positive bacteria, and has several unique structural features different from other spirotetronates. Here we describe identification and characterization of the maklamicin biosynthetic (mak) gene cluster through draft genome sequencing, genomic library screening, and gene disruption. Sequence analysis revealed that a plausible maklamicin cluster resides in a 152. kb DNA region encoding 46 open reading frames, 24 of which can be assigned roles in the biosynthesis of polyketide backbone, spirotetronate or peripheral moieties, self-resistance and the regulation of maklamicin production. Disruption of the polyketide synthase (PKS) genes makA1 or makA4 resulted in a complete loss of maklamicin production, indicating that the type I modular PKS system is responsible for the biosynthesis of maklamicin. The mak gene cluster contained a set of biosynthetic genes for the formation of a tetronate moiety, which were found to be highly conserved in the gene clusters for spirotetronate antibiotics. Based on the estimated biosynthetic genes, we propose the biosynthetic pathway for maklamicin. Our findings provide not only insights on the biosynthetic mechanism of the unique structures in maklamicin, but also useful information to facilitate a comparative analysis of the spirotetronate biosynthetic pathways to expand the structural repertoire.
ISSN: 09445013
Appears in Collections:Scopus 2011-2015

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