2. Academic Validation
  3. Deciphering the late steps of rifamycin biosynthesis

Deciphering the late steps of rifamycin biosynthesis

  • Nat Commun. 2018 Jun 14;9(1):2342. doi: 10.1038/s41467-018-04772-x.
Feifei Qi 1,  Chao Lei 2,  Fengwei Li 1,  Xingwang Zhang 1,  Jin Wang 2,  Wei Zhang 1,  Zhen Fan 2,  Weichao Li 2,  Gong-Li Tang 3,  Youli Xiao 4 5,  Guoping Zhao 2 6,  Shengying Li 7 8
Affiliations

Affiliations

  • 1 Shandong Provincial Key Laboratory of Synthetic Biology, CAS Key Laboratory of Biofuels, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong, 266101, China.
  • 2 CAS Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, China.
  • 3 State Key Laboratory of Bio-Organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 200032, Shanghai, China.
  • 4 CAS Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, China. ylxiao@sibs.ac.cn.
  • 5 University of Chinese Academy of Sciences, 100049, Beijing, China. ylxiao@sibs.ac.cn.
  • 6 University of Chinese Academy of Sciences, 100049, Beijing, China.
  • 7 Shandong Provincial Key Laboratory of Synthetic Biology, CAS Key Laboratory of Biofuels, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong, 266101, China. lishengying@qibebt.ac.cn.
  • 8 University of Chinese Academy of Sciences, 100049, Beijing, China. lishengying@qibebt.ac.cn.
PMID: 29904078 DOI: 10.1038/s41467-018-04772-x
Abstract

Rifamycin-derived drugs, including rifampin, rifabutin, rifapentine, and rifaximin, have long been used as first-line therapies for the treatment of tuberculosis and Other deadly infections. However, the late steps leading to the biosynthesis of the industrially important rifamycin SV and B remain largely unknown. Here, we characterize a network of reactions underlying the biosynthesis of rifamycin SV, S, L, O, and B. The two-subunit Transketolase Rif15 and the Cytochrome P450 enzyme Rif16 are found to mediate, respectively, a unique C-O bond formation in rifamycin L and an atypical P450 ester-to-ether transformation from rifamycin L to B. Both reactions showcase interesting chemistries for these two widespread and well-studied Enzyme families.

Figures
Products