Influence of increased dissolved oxygen concentration on the formation of secondary metabolites by manumycin-producing Streptomyces parvulus.

The influence of increased dissolved O2 concentrations (DOC) on cell growth and production of the secondary metabolite manumycin by a strain of Streptomyces parvulus (Tu 64) was investigated in a stirred tank fermentor. DOC is given as the O2 partial pressure (po2) in the gas phase in an equilibrium state with the liquid phase. Growth of S. parvulus was not influenced up to DOC equivalent to po2 = 1260 mbar. At po2 = 2205 mbar the maximum biomass concentration was lowered by 40%. Production of manumycin was markedly influenced by DOC and reached the maximal concentration at po2 = 315 mbar. At increased DOC three new metabolites were observed. Two of them, 64p-A and 64p-B, were identified as carboxamides, which represent the branched side chain of the manumycin molecule and a derivative with a shorter chain length. The third metabolite, 64p-C, was a manumycin derivative containing an aromatic ring system. Feeding of glycerol during the production phase increased the total yield and showed a similar effect of DOC. Since DOC has significant regulation effects on product formation and selectivity, it should be used as a major parameter in development strategies of aerobic microbial processes.