REGULATION OF SECONDARY METABOLITE BIOSYNTHESIS BY SEQUENTIAL PROCESSES OF PHOSPHATE LIMITATION AND PHOSPHATE RELEASE

Abstract

Usually, fermentations of secondary metabolites are carried out in the presence of phosphate levels suboptimal for growth. The onset of product formation coincides with the depletion of dissolved inorganic orthophosphate in fermentations of the macrolide turimycin, the aminocyclitol streptomycin, and the streptothricin-type antibiotic nourseothricin. As far as fermentations of secondary metabolites are concerned, it may be mainly the availability of phosphate ion (Pi) that controls respiration, ATP synthesis, and the transport of substrates in the mycelium. This chapter presents results that demonstrate that depletion of phosphate from the medium of growing cultures causes the onset of a special stationary phase development, which can be characterized by the vigorous formation of secondary metabolites and dephosphorylating enzymes in the cells and their secretion into the medium. To realize a high rate of antibiotic biosynthesis, this particular state needs to be maintained over the whole fermentation time. This goal can be achieved either by the use of a donor of phosphate enabling rate-limiting release of Pi or by continuous feeding of low concentrations of inorganic phosphate to the medium.