Nucleocidin, a secondary metabolite of Streptomyces calvus (1), is a derivative of adenosine that contains 4’-fluorine and 5’-O-sulfamate groups. Both substituents are rarely observed in natural products. A minimal biosynthetic gene cluster has yet to be defined for nucleocidin, and at least 24 genes appear to be involved. To date, only two functions have been assigned, neither of which are directly involved in sulfamate biosynthesis or fluorination (2, 3). In this presentation, we present biosynthetic studies on two newly discovered producers of nucleocidin, Streptomyces virens B-24331 and Streptomyces aureorectus B-24301 (4). Both strains are shown to be significantly (up to 30-fold) better producers of nucleocidin than S. calvus. Gene disruption experiments in S. virens have identified, for the first time, genes differentially impacting sulfmate and 4’-fluorine biosynthesis. These and additional results will be presented.
References :
(1) Zhu, X. M., et al., Biosynthesis of the Fluorinated Natural Product Nucleocidin in Streptomyces calvus Is Dependent on the bldA-Specified Leu-tRNA(UUA) Molecule. ChemBioChem 2015, 16, 2498–2506.
(2) Feng, X., et al. Two 3’-O-b-glucosylated nucleoside fluorometabolites related to nucleocidin in Streptomyces calvus. Chem. Sci. 2019, 10, 9501-9505.
(3) Ngivprom, U., et al. Characterization of NucPNP and NucV involved in theearly steps of nucleocidin biosynthesis in Streptomyces calvus. RSC Adv., 2021, 11, 3510-3515.
(4) Chen, Y., et al., Streptomyces aureorectus DSM 41692 and Streptomyces virens DSM 41465 are producers of the antibiotic nucleocidin and 4’-fluoroadenosine is identified as a co-product. Org. Biomol. Chem. 2021, DOI: 10.1039/d1ob01898a.
