Engineering precursor flow for increased erythromycin production in Aeromicrobium erythreum

被引：45

作者：

Reeves, AR ^{[1
]}

Cernota, WH ^{[1
]}

Brikun, IA ^{[1
]}

Wesley, RK ^{[1
]}

Weber, JM ^{[1
]}

机构：

[1] Fermalog Inc, Chicago, IL 60612 USA

来源：

METABOLIC ENGINEERING | 2004年 / 6卷 / 04期

关键词：

methylmalonyl-CoA mutase; coenzyme B-12; metabolic engineering; strain improvement; mutB; cobA; erythromycin;

D O I：

10.1016/j.ymben.2004.03.003

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页码：300 / 312

页数：13

共 55 条

[51] ORGANIZATION OF A CLUSTER OF ERYTHROMYCIN GENES IN SACCHAROPOLYSPORA-ERYTHRAEA [J].