Emerging Concepts of Secondary Metabolism in Actinomycetes.

Abstract

Secondary metabolism in actinomycetes is brought on by exhaustion of a nutrient and/or by a growth rate decrease. These events generate signals which effect a cascade of regulatory events resulting in chemical differentiation (secondary metabolism) and morphological differentiation (morphogenesis). The signal is often a low molecular weight butyrolactone inducer (autoregulatory factor) which acts by negative control, i.e. by binding to a regulatory protein (repressor protein / receptor protein) which prevents secondary metabolism and morphogenesis during rapid growth and nutrient sufficiency. Nutrient/growth rate signals presumably activate a “master gene” which either acts at the level of translation by encoding a rare tRNA, or by encoding a positive transcription factor. Such master genes control both secondary metabolism and morphogenesis. At the second level of regulatory hierarchy are genes which control one branch of the cascade, i.e. either secondary metabolism or morphogenesis but not both. In the secondary metabolism branch, genes at the third level control formation of particular groups of secondary metabolites. At the fourth level are genes which control smaller groups, and finally, fifth level genes control individual biosynthetic pathways; these are usually positively acting but at least one acts negatively. These are also several levels of hierarchy on the morphogenesis branch. The second level includes genes which control aerial mycelium formation plus all the conidial genes lower in the cascade. Each third level locus controls a particular stage of conidiation (e.g. coiling, septation, wall thickening, spore maturation or spore pigmentation). Many of the these conidiation loci are complex, containing a number of genes; at least two code for sigma factors. Feedback regulation also plays a role in secondary metabolite control.