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Biosynthesis of antibiotic chuangxinmycin from Actinoplanes tsinanensis

Biosynthesis of antibiotic chuangxinmycin from

Actinoplanes tsinanensis

Yuanyuan Shi;Zhibo Jiang;Xingxing Li;Lijie Zuo;Xuan Lei;Liyan Yu;Linzhuan Wu;Jiandong Jiang;Bin Hong

【期刊名称】《药学学报(英文版)》

【年(卷),期】2018(008)002

【摘要】Chuangxinmycin is an antibiotic isolated from Actinoplanes tsinanensis CPCC 200056 in the 1970s with a novel indole-dihydrothiopyran heterocyclic skeleton.Chuangxinmycin showed in vitro antibacterial activity and in vivo efficacy in mouse infection models as well as preliminary clinical trials.But the biosynthetic pathway of chuangxinmycin has been obscure since its discovery.Herein,we report the identification of a stretch of DNA from the genome of A.tsinanensis CPCC 200056 that encodes genes for biosynthesis of chuangxinmycin by bioinformatics analysis.The designated cxn cluster was then confirmed to be responsible for chuangxinmycin biosynthesis by direct cloning and heterologous expressing in Streptomyces coelicolor M1146.The cytochrome P450 CxnD was verified to be involved in the dihydrothiopyran ring closure reaction by the identification of seco-chuangxinmycin in S.coelicolor M1146 harboring the cxn gene cluster with an inactivated cxnD.Based on these results,a plausible biosynthetic pathway for chuangxinmycin biosynthesis was proposed,by hijacking

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