Characterization of the coformycin biosynthetic gene cluster in Streptomyces kaniharaensis

• DOI: 10.1073/pnas.2000111117
• Publication Date: 2020-04-29T23:57:00Z
• Authors: Daan Ren; Mark W. Ruszczycky; Yeonjin Ko; Shao-An Wang; Yasushi Ogasawara; Minje Kim; Hung-wen Liu
• Keywords: Deoxycoformycin

Significance Coformycin and pentostatin are potent nucleoside inhibitors of adenosine deaminase with anticancer activity due to their structurally unique 1, 3-diazepine nucleobases. Herein, the biosynthetic pathway coformycin is reconstituted in vitro, demonstrating that it directly overlaps early stages l -histidine biosynthesis. The key branch point between pathways involves a seven-membered ring cyclization reaction likely proceeds via Dieckmann retro-aldol elimination. This catalyzed an ATP-dependent manner, although phosphorylation substrate does not appear be part catalytic cycle. suggests regulatory role for ATP may important modulating competition shared resources metabolic processes L-histidine