Guanosine 5′-diphosphate 3′-diphosphate (ppGpp) and clavulanic acid production in Streptomyces clavuligerus

Streptomyces clavuligerus produced clavulanic acid under defined glycerol and phosphate growth-limiting batch fermentations. Clavulanic acid was not produced under nitrogen-limiting conditions. The highly phosphorylated nucleotide guanosine 5'-diphosphate 3'-diphosphate (ppGpp) accumulated to low levels during the early stages of mycelial growth under glycerol-limitation, and to high levels under phosphate-limitation. Transcription of the clavaminate synthase gene could be correlated with ppGpp production under phosphate-limiting conditions but not in glycerol-limited fermentation.