Antibiotic Regulatory Genes and Metabolic Engineering

DESCRIPTION (provided by applicant): Strain improvement of commercial fermentations helps to reduce the cost of production of existing pharmaceuticals and helps industry to meet the growing demands for desperately needed new products, such as antibiotics, that can be produced in large enough quantities and at prices the public can afford. This project focuses on strain improvement in a bacterium that generates a widely used antibiotic, erythromycin. This bacterium, Saccharopolyspora erythraea, is a member of the Actinomycete family and is widely used in academic research and industry, making it an excellent model system for this work. The objective of this project is to identify and manipulate genes responsible for controlling erythromycin yield during fermentation. In Phase I a mutagenic plasmid insertion library was created in Sac. erythraea and four classes of morphological and pigmentation mutants were found using a simple visual screen. Three classes of mutants were found that showed significant increases in erythromycin production. An efficient plasmid rescue technique allowed recovery of the integrated plasmid and DNA sequence analysis of the plasmid insert. In Phase II the screening and mutant analysis will continue. The strain improvement genes found could have general application to strain improvement programs for other drugs. PROPOSED COMMERCIAL APPLICATION: Not Available