Characterization of the coformycin biosynthetic gene cluster in Streptomyces kaniharaensis
| Autor: | Mark W. Ruszczycky, Minje Kim, Hung-wen Liu, Yasushi Ogasawara, Shao-An Wang, Yeonjin Ko, Daan Ren |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Multidisciplinary Ribonucleotide biology 010405 organic chemistry Chemistry 030106 microbiology Dehydrogenase 01 natural sciences 0104 chemical sciences Dephosphorylation Coformycin 03 medical and health sciences chemistry.chemical_compound Adenosine deaminase Biochemistry Biosynthesis Gene cluster biology.protein Adenosine triphosphate |
| Zdroj: | Proceedings of the National Academy of Sciences. 117:10265-10270 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | 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- 5 ′ -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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|