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Qi, Feifei; Lei, Chao; Li, Fengwei; Zhang, Xingwang; Wang, Jin; Zhang, Wei; Fan, Zhen; Li, Weichao; Tang, Gong-Li; Xiao, Youli; Zhao, Guoping; Li, Shengying
Nature communications, 06/2018, Volume: 9, Issue: 1Journal Article
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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