Guanosine 5'-diphosphate 3'-diphosphate (ppGpp), guanosine 5'-diphosphate 3'-monophosphate (ppGp) and antibiotic production in Streptomyces clavuligerus

Streptomyces clavuligerus produced cephamycin C under all nutrient limitations investigated in batch culture, whilst clavulanic acid was produced under phosphate and carbon limitations. Guanosine 5′-diphosphate 3′-diphosphate (ppGpp) was produced at very low levels in all fermentations, prior to the detection of cephamycin C in the fermentation broth. Guanosine 5′-diphosphate 3′-monophosphate (ppGp) was observed at high levels in all fermentations; it appeared following a downturn in nutrient levels and immediately prior to detection of isopenicillin N synthase (IPNS). ppGp was detected following nutritional shiftdown by amino acid depletion and it was not produced via degradation of ppGpp. The results point to a possible role for ppGp in the regulation of cephamycin production in S. clavuligerus.