Isolation of 5'- O-sulfamyladenosine and related 3'- O-β-glucosylated adenosines from the nucleocidin producer Streptomyces calvus

Abstract

The isolation of three adenosine based metabolites 6-8 from Streptomyces calvus is reported. The metabolites are structurally related to the fluorine containing antibiotic nucleocidin 1 and two recently identified glycosylated fluoroadenosines 2 and 3, however in this case the three metabolites do not contain a fluorine, suggesting that the biosynthetic enzymes to the fluorometabolites also process their non-fluorinated counterparts.

Fig. 1. Known 4′-fluoro- and 5′-O-sulfamyl-adenosine natural products 1–6.

Fig. 2. 3′-O-β-Glucosylated adenosines 7 and 8 of S. clavus.

Fig. 3. HPLC profiles of 7, 8 and 5′-O-sulfamyladenosine 6.

Fig. 4. HRMS and MS² spectra of 7, 8 and 5′-O-sulfamyladenosine 6.

Fig. 5. Tabulated kinetic data of NucGT with adenosine or 5′-O-sulfamyladenosine 6 to generate 7 and 8 respectively. Michaelis–Menten kinetics curve are shown for NucGT with (lower left) adenosine or (lower right) 5′-O-sulfamyladenosine 6.

Fig. 6. Putative relationships between fluoro and nonfluoro metabolites during nucleocidin 1 biosynthesis in S. calvus. The substrate for fluorination is unknown. All structures have been isolated from S. calvus except candidate 9. Solid arrows represent biochemically validated steps involving NucGT and the glucosidase enzymes NucGS. Broken arrows remain to be validated biochemically.