Chin. J. Org. Chem. ›› 2017, Vol. 37 ›› Issue (12): 3262-3266.DOI: 10.6023/cjoc201708007 Previous Articles     Next Articles



周弘扬a, 罗光彩a, 张转b, 周强b, 翟鑫a, 唐功利a,b   

  1. a 沈阳药科大学中药学院 基于靶点的药物设计与研究教育部重点实验室 沈阳 110016;
    b 中国科学院上海有机化学研究所 生命有机化学国家重点实验室 上海 200032
  • 收稿日期:2017-08-04 修回日期:2017-09-01 发布日期:2017-09-26
  • 通讯作者: 翟鑫, 唐功利;
  • 基金资助:


Cooperation of Two Biosynthetic Gene Clusters in the Biosynthesis of New Anthracycline Polyketide

Zhou Hongyanga, Luo Guangcaia, Zhang Zhuanb, Zhou Qiangb, Zhai Xina, Tang Gong-Lia,b   

  1. a Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016;
    b State Key Laboratory of Bio-Organic and Natural Product Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032
  • Received:2017-08-04 Revised:2017-09-01 Published:2017-09-26
  • Contact: 10.6023/cjoc201708007;
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 81373307) and the Science and Technology Comission Shanghai Municipality (No. 14XD1404500).

Micromonospora sp. TP-A0468 harbors multiple biosynthetic gene clusters encoding the biosynthesis of secondary metabolites, including kosinostatin (KST) and rifamycins. In our study on the biosynthesis of KST, a new anthracycline polyketide 554B was isolated from the kstB1 deletion mutant △kstB1 and identified as shunt product of KST pathway bearing 4-acetyl-2,3,6-deoxyhexosyl moiety. The unexpected elimination of C-3' hydroxyl suggests a 3,4-dehydratase involved in the biosynthesis of 554B, of which the encoding gene was proposed to located beyond the kst gene cluster. Bioinformatic analysis revealed orf6 of rifamycin biosynthetic gene cluster (rif) was the candidate of required 3,4-dehydratase gene. Deletion of orf6 abolished the production of 554B, confirming the involvement of orf6 in the biosynthesis of 554B. Our study attributed orf6 to the origin of 2,3,6-deoxyhexosyl and unveiled the cooperation between biosynthetic gene clusters in Micromonospora sp. TP-A0468.

Key words: anthracycline, hexose 3,4-dehydratase, biosynthesis, gene cluster cooperation