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


ABSTRACT: 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.

SUBMITTER: Ngivprom U 

PROVIDER: S-EPMC8694150 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Characterization of NucPNP and NucV involved in the early steps of nucleocidin biosynthesis in <i>Streptomyces calvus</i>.

Ngivprom Utumporn U   Kluaiphanngam Surayut S   Ji Wenjuan W   Siriwibool Siriwalee S   Kamkaew Anyanee A   Ketudat Cairns James R JR   Zhang Qi Q   Lai Rung-Yi RY  

RSC advances 20210115 6


Nucleocidin 1 produced by <i>Streptomyces calvus</i> 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 <i>nucPNP</i> gene, which was initially annotated as <i>orf206</i> and encodes a putative purine nucleoside phosphorylase, is essential for nucleocidin production. In this study, we performed <i>in vitro</i> assays and showed NucPNP pr  ...[more]

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