The objective of the grant is to define aspects of the genetic regulation of Streptomyces coelicolor morphological and physiological differentiation. The emphasis is on the transition from the vegetative to the differentiated colony, as manifested by onset of antibiotic synthesis and by the growth of prespore aerial hyphae. The specific aims are: 1. Genetic and phenotypic Characterization of the new developmental mutants. We will refine the genetic characterization of the newly identified absA, bldH loci by performing complementation and fine-structure mapping studies. We will also continue the phenotypic characterization of the bld mutants. 2. Cloning and molecular characterization of the new developmental genes absA, bldG and bldH. We will clone these genes and use the cloned alleles for complementation studies and for sequencing the wild-type and mutant alleles. This genetic and molecular analysis of the abs and bld genes promises to contribute not only to our understanding of microbial multicellular development and differentiation, but also to the potential for rational manipulation of naturally occurring antibiotic synthesis.
