Biosynthesis of sinefungin by cell-free extract of Streptomyces incarnatus NRRL 8089.

The formation of sinefungin an antifungal and anti-parasitic nucleoside antibiotic was demonstrated in cell-free extracts from Streptomyces incarnatus. Incorporation studies as well as HPLC analysis showed that the immediate biosynthetic precursors of the antibiotic are L-arginine and ATP. The biosynthesis was optimal when the cell-free extract was prepared from 72 hours mycelium and incubated at least 80 minutes with arginine and ATP. The presence of dithiothreitol, pyridoxal phosphate and Mg2+ in the incubation mixture was also necessary. When a membrane fraction was incubated under the same conditions with ATP and L-arginine, sinefungin production was not observed. A working hypothesis is put forward to explain the biosynthesis of this antibiotic.