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Title: 29-Deoxymaklamicin, a new maklamicin analogue produced by a genetically engineered strain of Micromonospora sp. NBRC 110955
Authors: Ratama Daduang
Shigeru Kitani
Yuri Sudoh
Ivy Grace Umadhay Pait
Arinthip Thamchaipenet
Haruo Ikeda
Yasuhiro Igarashi
Takuya Nihira
Osaka University
Hyphagenesis Inc.
Kasetsart University
Kitasato University
Toyama Prefectural University
Mahidol University
Keywords: Biochemistry, Genetics and Molecular Biology;Chemical Engineering;Immunology and Microbiology
Issue Date: 1-Dec-2015
Citation: Journal of Bioscience and Bioengineering. Vol.120, No.6 (2015), 608-613
Abstract: © 2015 The Society for Biotechnology, Japan. Maklamicin is a spirotetronate-class antibiotic produced by Micromonospora sp. NBRC 110955, and a polyketide assembly line and a glycerate utilization system are involved in its biosynthesis. One tailoring step in the biosynthesis is predicted to be post-polyketide synthase (PKS) modification, which seems to be catalysed by putative cytochrome P450 monooxygenases, MakC2 and/or MakC3. In this study, we characterized makC2 and makC3 in the biosynthesis of maklamicin and identified a new maklamicin analogue from a makC2 disruptant. Gene deletion of makC2 resulted in the complete loss of maklamicin production with concomitant accumulation of a new compound (29-deoxymaklamicin), while gene deletion of makC3 did not affect the maklamicin production, indicating that 29-deoxymaklamicin is an intermediate in the biosynthetic pathway of maklamicin and should serve as the substrate of MakC2. 29-Deoxymaklamicin showed strong-to-modest anti-microbial activity against gram-positive bacteria. The fact that Streptomyces avermitilis heterologously expressing makC2 successfully converted 29-deoxymaklamicin into maklamicin confirmed that MakC2 is the final-step hydroxylase in the formation of mature maklamicin.
ISSN: 13474421
Appears in Collections:Scopus 2011-2015

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