期刊
METABOLIC ENGINEERING
卷 6, 期 4, 页码 300-312出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymben.2004.03.003
关键词
methylmalonyl-CoA mutase; coenzyme B-12; metabolic engineering; strain improvement; mutB,cobA; erythromycin
资金
- NIGMS NIH HHS [GM58943] Funding Source: Medline
Metabolic engineering technology for industrial microorganisms is under development to create rational, more reliable, and more cost-effective approaches to strain improvement. Strain improvement is a critical component of the drug development process, yet the genetic basis for high production by industrial microorganisms is still a mystery. In this study, a search was begun for genetic modifications critical for high-level antibiotic production. The model system used was erythromycin production studied in the unicellular actinomycete, Aeromicrobium erythreum. A tagged-mutagenesis approach allowed reverse engineering of improved strains, revealing two genes, mutB and cobA, in the primary metabolic branch for methylmalonyl-CoA utilization, Knockouts in these genes created a permanent metabolic switch in the flow of methylmalonyl-CoA, from the primary branch into a secondary metabolic branch, driving erythromycin overproduction. The model provides insights into the regulation and evolution of secondary metabolism. (C) 2004 Elsevier Inc. All rights reserved.
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