Heterologous expression of methylmalonyl-CoA carboxyltransferase to improve the fatty acid production in Escherichia coli

Abstract

Microbial production of oleochemicals has been received an attention due to depletion of the resource. Fatty acid-derived chemicals are usually produced via microbial fatty acid synthesis pathway since almost microbes harbor at least a pathway to provide a major component of the cell membranes and their derivatives. However, fatty acid metabolism in microorganism is controlled by a complex and tightly-regulated network. The expression of acetyl-CoA carboxylases (ACCs) catalyzing the first step of fatty acid synthesis pathway is regulated at the levels of its transcription, translation, and enzyme activity. The highly regulated systems result in maintaining the intracellular concentration of malonylCoA at a certain level. Here we describe a metabolic engineering strategy to improve both intracellular malonyl-CoA pool and fatty acid production by avoiding the tight regulation of the rate-limiting step. The genes encoding methylmalonyl-CoA carboxyltransferase from Propionibacterium freudenreichii shermanii and Veillonella parvula are expressed in E. coli. Engineered cells produce higher fatty acid production than ACC overexpressing strain. This result indicates that the synthetic pathway to bypass severe regulation can directly improve the production of the target compounds.