29-Deoxymaklamicin, a new maklamicin analogue produced by a genetically engineered strain of Micromonospora sp. NBRC 110955

详细信息    查看全文

• 作者：Ratama Daduang¹ ; Shigeru Kitani¹ ; Yuri Sudoh² ; Ivy Grace Umadhay Pait¹ ; Arinthip Thamchaipenet³ ; Haruo Ikeda⁴ ; Yasuhiro Igarashi⁵ ; Takuya Nihira¹ ; ⁶ ; ^{nihira@icb.osaka-u.ac.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Micromonospora ; Spirotetronate-class antibiotics ; Maklamicin ; Cytochrome P450 ; Hydroxylation
• 刊名：Journal of Bioscience and Bioengineering
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：120
• 期：6
• 页码：608-613
• 全文大小：724 K

文摘

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.