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Abstract

Grant Number: 5R44GM058943-03
PI Name: REEVES, ANDREW R.
PI Email: andrew.reeves@fermalogic.com
PI Title:
Project Title: Antibiotic Regulatory Genes and Metabolic Engineering

Abstract: 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

Thesaurus Terms:
Actinomycetales, bacterial genetics, erythromycin, gene targeting, genetic library, genetic screening, microorganism mass culture, microorganism metabolism, regulatory gene
biological product, gene mutation, genetic strain, plasmid
biotechnology

Institution: FERMALOGIC, INC.
CHICAGO TECHNOLOGY PARK
CHICAGO, IL 60612
Fiscal Year: 2002
Department:
Project Start: 15-AUG-1999
Project End: 31-AUG-2003
ICD: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
IRG: ZRG1


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