RRC ID 71368
著者 Yu L, Zhou W, She Y, Ma H, Cai YS, Jiang M, Deng Z, Price NPJ, Chen W.
タイトル Efficient biosynthesis of nucleoside cytokinin angustmycin A containing an unusual sugar system.
ジャーナル Nat Commun
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.
巻・号 12(1)
ページ 6633
公開日 2021-11-17
DOI 10.1038/s41467-021-26928-y
PII 10.1038/s41467-021-26928-y
PMID 34789759
PMC PMC8599513
MeSH Adenosine / analogs & derivatives* Adenosine / biosynthesis Adenosine / chemistry Bacterial Proteins / genetics Bacterial Proteins / metabolism Biosynthetic Pathways Cytokinins / biosynthesis* Cytokinins / chemistry Dehydration Escherichia coli / genetics Escherichia coli / metabolism Fermentation Molecular Structure Multigene Family Nucleosides / biosynthesis* Nucleosides / chemistry Recombinant Proteins / genetics Recombinant Proteins / metabolism Streptomyces / enzymology Streptomyces / genetics
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最多言及媒体 Patent(IFI CLAIMS)
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過去6か月間でのオルトメトリクス指標の変動値 0.0
リソース情報
一般微生物 JCM4053