Publication: 29-Deoxymaklamicin, a new maklamicin analogue produced by a genetically engineered strain of Micromonospora sp. NBRC 110955
Issued Date
2015-12-01
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ISSN
13474421
13891723
13891723
Other identifier(s)
2-s2.0-84946486196
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Bioscience and Bioengineering. Vol.120, No.6 (2015), 608-613
Suggested Citation
Ratama Daduang, Shigeru Kitani, Yuri Sudoh, Ivy Grace Umadhay Pait, Arinthip Thamchaipenet, Haruo Ikeda, Yasuhiro Igarashi, Takuya Nihira 29-Deoxymaklamicin, a new maklamicin analogue produced by a genetically engineered strain of Micromonospora sp. NBRC 110955. Journal of Bioscience and Bioengineering. Vol.120, No.6 (2015), 608-613. doi:10.1016/j.jbiosc.2015.04.004 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/35344
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Title
29-Deoxymaklamicin, a new maklamicin analogue produced by a genetically engineered strain of Micromonospora sp. NBRC 110955
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.