論文

査読有り 国際誌
2020年5月12日

Characterization of the coformycin biosynthetic gene cluster in Streptomyces kaniharaensis.

Proceedings of the National Academy of Sciences of the United States of America
  • Daan Ren
  • ,
  • Mark W Ruszczycky
  • ,
  • Yeonjin Ko
  • ,
  • Shao-An Wang
  • ,
  • Yasushi Ogasawara
  • ,
  • Minje Kim
  • ,
  • Hung-Wen Liu

117
19
開始ページ
10265
終了ページ
10270
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1073/pnas.2000111117

Coformycin and pentostatin are structurally related N-nucleoside inhibitors of adenosine deaminase characterized by an unusual 1,3-diazepine nucleobase. Herein, the cof gene cluster responsible for coformycin biosynthesis is identified. Reconstitution of the coformycin biosynthetic pathway in vitro demonstrates that it overlaps significantly with the early stages of l-histidine biosynthesis. Committed entry into the coformycin pathway takes place via conversion of a shared branch point intermediate to 8-ketocoformycin-[Formula: see text]-monophosphate catalyzed by CofB, which is a homolog of succinylaminoimidazolecarboxamide ribotide (SAICAR) synthetase. This reaction appears to proceed via a Dieckmann cyclization and a retro-aldol elimination, releasing ammonia and D-erythronate-4-phosphate as coproducts. Completion of coformycin biosynthesis involves reduction and dephosphorylation of the CofB product, with the former reaction being catalyzed by the NADPH-dependent dehydrogenase CofA. CofB also shows activation by adenosine triphosphate (ATP) despite the reaction requiring neither a phosphorylated nor an adenylated intermediate. This may serve to help regulate metabolic partitioning between the l-histidine and coformycin pathways.

リンク情報
DOI
https://doi.org/10.1073/pnas.2000111117
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32350138
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229688

エクスポート
BibTeX RIS