Study of the morphological and biochemical differentiation of Saccharopolyspora erythraea.

The aim of this study was to identify and measure areas of physiology relevant to the initiation of secondary metabolism and spore formation. It was discovered that the growth kinetics of Saccharopolyspora erythraea in a liquid culture environment were dependent on the type of nutrient limitation the organism was exposed to. Sacc. erythraea was able to produce erythromycin and formed structures which had properties similar to those of spores (designated 'sonic resistant units' in this thesis) in a nitrogen limited medium but, would produce erythromycin but no 'sonic resistant units' in a carbon limited medium. This resulted in two liquid culture systems, one which supported the formation of 'sonic resistant units' and one which did not, and thus enabled the comparison of the conditions which resulted in sporulation or secondary metabolism. The measurement of the rate of DNA, RNA and protein synthesis showed distinct profiles of synthesis in both media. Measurements of these rates in Streptomyces hygroscopicus showed similar profiles in the same media suggesting that the behaviour of the macromolecular synthesis rates in different nutrient limiting conditions might be applicable to streptomycetes in general. A change in macromolecular synthesis rate was implicated in inducing secondary metabolism. Antibiotics were used to modulate these rates in an attempt to induce secondary metabolism. Results from these experiments suggested the possible role of the intracellular concentration of charged and uncharged tRNA in induction of antibiotic synthesis. This relationship implies an analogy between the stringent response and the physiology of the induction of secondary metabolism. The formation of spores ('sonic resistant units') did not appear to be induced by changes in macromolecular synthesis rate or changes in tRNA levels or ratio. However, it was evident that the rates of macromolecular synthesis increased during the production of spores and this implied that it is the action of some intracellular agent that is inducing macromolecular synthesis to fuel the spore forming process