期刊
JOURNAL OF BIOSCIENCE AND BIOENGINEERING
卷 120, 期 6, 页码 608-613出版社
SOC BIOSCIENCE BIOENGINEERING JAPAN
DOI: 10.1016/j.jbiosc.2015.04.004
关键词
Micromonospora; Spirotetronate-class antibiotics; Maklamicin; Cytochrome P450; Hydroxylation
资金
- JSPS [24310157, 24651243, 24780071]
- Ministry of Education, Culture, Sports, and Technology of Japan
- Grants-in-Aid for Scientific Research [24651243, 24780071] Funding Source: KAKEN
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. (c) 2015, The Society for Biotechnology, Japan. All rights reserved.
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