The anti-tuberculous rifamycins belong to naphthalenic ansamycin based on the structure of aromatic chromophore.Herein,we explored the post-polyketide synthase(PkS)modifications in the biosynthesis of 16-demethyl-rifa...The anti-tuberculous rifamycins belong to naphthalenic ansamycin based on the structure of aromatic chromophore.Herein,we explored the post-polyketide synthase(PkS)modifications in the biosynthesis of 16-demethyl-rifamycins via gene knockout,complementation and in vitro enzyme assays.The collective evidences showed that i)the aromatization of 8-hydroxyl-7,8-dihydronaphtoquinone was accomplished by the combined action of two dehydrogenases,Rifs and Rif;i)the acetylation and methylation of the macrocycle was carried out on naphthoquinone intermediates in preference to naphthol,by Rif-Orf20 and Rif-Orf14,respectively ii)the presence of Rifs/T homologs in ansamycin biosynthetic gene clusters corresponds to the dehydrogenation aromatization mode of dihydronaphthalene.These findings cast new insights into the naphthalene formation and post-PkS modification of ansamycins.展开更多
基金We thank the financial support from the National Natural Science Foundation of China(22137009 and 21907067).
文摘The anti-tuberculous rifamycins belong to naphthalenic ansamycin based on the structure of aromatic chromophore.Herein,we explored the post-polyketide synthase(PkS)modifications in the biosynthesis of 16-demethyl-rifamycins via gene knockout,complementation and in vitro enzyme assays.The collective evidences showed that i)the aromatization of 8-hydroxyl-7,8-dihydronaphtoquinone was accomplished by the combined action of two dehydrogenases,Rifs and Rif;i)the acetylation and methylation of the macrocycle was carried out on naphthoquinone intermediates in preference to naphthol,by Rif-Orf20 and Rif-Orf14,respectively ii)the presence of Rifs/T homologs in ansamycin biosynthetic gene clusters corresponds to the dehydrogenation aromatization mode of dihydronaphthalene.These findings cast new insights into the naphthalene formation and post-PkS modification of ansamycins.
