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  • Title: 29-Deoxymaklamicin, a new maklamicin analogue produced by a genetically engineered strain of Micromonospora sp. NBRC 110955.
    Author: Daduang R, Kitani S, Sudoh Y, Grace Umadhay Pait I, Thamchaipenet A, Ikeda H, Igarashi Y, Nihira T.
    Journal: J Biosci Bioeng; 2015 Dec; 120(6):608-13. PubMed ID: 25939549.
    Abstract:
    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.
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