Metabolic engineering of Escherichia coli for alpha-farnesene production

Abstract

Sesquiterpenes are important materials in pharmaceuticals and industry. Metabolic engineering has been successfully used to produce these valuable compounds in microbial hosts. However, the microbial potential of sesquiterpene production is limited by the poor heterologous expression of plant sesquiterpene synthases and the deficient FPP precursor supply. In this study, we engineered E. coli to produce alpha-farnesene using a codon-optimized alpha-farnesene synthase and an exogenous MVA pathway. Codon optimization of alpha-farnesene synthase improved both the synthase expression and alpha-farnesene production. Augmentation of the metabolic flux for FPP synthesis conferred a 1.6- to 48.0-fold increase in alpha-farnesene production. An additional increase in alpha-farnesene production was achieved by the protein fusion of FPP synthase and alpha-farnesene synthase. The engineered E. coli strain was able to produce 380.0 mg/L of alpha-farnesene, which is an approximately 317-fold increase over the initial production of 1.2 mg/L. (C) 2011 Elsevier Inc. All rights reserved.