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Efficient biosynthesis of nucleoside cytokinin angustmycin A containing an unusual sugar system

ABSTRACT: Angustmycin A has anti-mycobacterial and cytokinin activities, and contains an intriguing structure in which an unusual sugar with C5′-C6′ dehydration is linked to adenine via an N-glycosidic bond. However, the logic underlying the biosynthesis of this molecule has long remained obscure. Here, we address angustmycin A biosynthesis by the full deciphering of its pathway. We demonstrate that AgmD, C, A, E, and B function as d-allulose 6-phosphate 3-epimerase, d-allulose 6-phosphate pyrophosphokinase, adenine phosphoallulosyltransferase, phosphoribohydrolase, and phosphatase, respectively, and that these collaboratively catalyze the relay reactions to biosynthesize angustmycin C. Additionally, we provide evidence that AgmF is a noncanonical dehydratase for the final step to angustmycin A via a self-sufficient strategy for cofactor recycling. Finally, we have reconstituted the entire six-enzyme pathway in vitro and in E. coli leading to angustmycin A production. These results expand the enzymatic repertoire regarding natural product biosynthesis, and also open the way for rational and rapid discovery of other angustmycin related antibiotics. Angustmycin A is a nucleoside antibiotic having anti-mycobacterial and cytokinin activities. Here, the authors report the whole pathway leading to angustmycin A biosynthesis in Streptomyces and achieve the heterologous production of angustmycin A in E. coli.

SUBMITTER: Yu L

PROVIDER: S-EPMC8599513 | biostudies-literature |

REPOSITORIES: biostudies-literature

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