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.
D000241:Adenosine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000935:Antifungal Agents / Q000096:biosynthesis*; D001120:Arginine / Q000378:metabolism; D002474:Cell-Free System; D002851:Chromatography, High Pressure Liquid; D012440:Saccharomyces / Q000187:drug effects; D013302:Streptomyces / Q000378:metabolism*
D000935:Antifungal Agents; D000255:Adenosine Triphosphate; D001120:Arginine; D000241:Adenosine; C006235:sinefungin