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Deciphering the late steps of rifamycin biosynthesis.

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.

SUBMITTER: Qi F

PROVIDER: S-EPMC6002545 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Deciphering the late steps of rifamycin biosynthesis.

Qi Feifei F Lei Chao C Li Fengwei F Zhang Xingwang X Wang Jin J Zhang Wei W Fan Zhen Z Li Weichao W Tang Gong-Li GL Xiao Youli Y Zhao Guoping G Li Shengying S

Nature communications 20180614 1

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 f ...[more]

PMID: 29904078

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