Characterization of NucPNP and NucV involved in the early steps of nucleocidin biosynthesis in Streptomyces calvus

Autor: Wenjuan Ji, James R. Ketudat Cairns, Surayut Kluaiphanngam, Qi Zhang, Anyanee Kamkaew, Siriwalee Siriwibool, Rung-Yi Lai, Utumporn Ngivprom
Rok vydání: 2021
Předmět:
Zdroj: RSC Advances. 11:3510-3515
ISSN: 2046-2069
DOI: 10.1039/d0ra10878b
Popis: Nucleocidin 1 produced by Streptomyces calvus is one of five characterized natural products containing fluorine. It was discovered in 1956, but its biosynthesis is not yet completely resolved. Recently, the biosynthetic gene cluster of 1 was identified. The nucPNP gene, which was initially annotated as orf206 and encodes a putative purine nucleoside phosphorylase, is essential for nucleocidin production. In this study, we performed in vitro assays and showed NucPNP produced adenine 3 from methylthioadenosine (MTA) 2 and adenosine 4. We also showed the downstream enzyme, NucV annotated as adenine phosphoribosyltransferase (APRT), catalyzes AMP formation from adenine 3 and 5-phospho-α-D-ribose-1-diphosphate (PRPP) 5. However, the catalytic efficiency of NucV was much slower than its homolog ScAPRT involved in the biosynthesis of canonical purine nucleoside in the same strain. These results provide new insights in nucleocidin biosynthesis and could guide future research on organofluorine formation.
Databáze: OpenAIRE