Oxygen limitation can induce microbial secondary metabolite formation: investigations with miniature electrodes in shaker and bioreactor culture

Abstract

Summary: A miniature electrode was used to measure, for the first time, the time-dependent change in dissolved oxygen concentration of small-scale cultures of two actinomycete species at various aeration efficiencies in both complex and defined media. Erythromycin was produced in both oxygen-limited and oxygen-sufficient conditions in shaken flask and inclined tube cultures of Saccharopolyspora erythraea and a further, novel, secondary metabolite was produced only under oxygen limitation. In contrast, vancomycin was only produced in oxygen-sufficient cultures of Amycolatopsis orientalis. Similar results were obtained in batch bioreactor cultures. These findings indicate that oxygen limitation acts in an analogous manner to substrate limitation imposed by dissolved nutrients, stimulating secondary metabolite production in some cases and inhibiting it in others. The implications of these findings in screening programmes for novel secondary metabolites are discussed.