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
  • 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. [email protected].
  • 5. University of Chinese Academy of Sciences, 100049, Beijing, China. [email protected].
  • 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. [email protected].
  • 8. University of Chinese Academy of Sciences, 100049, Beijing, China. [email protected].
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.

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