Enhancing fatty acid ethyl ester production in Saccharomyces cerevisiae through metabolic engineering and medium optimization

ABSTRACT Biodiesels in the form of fatty acyl ethyl esters (FAEEs) are a promising next generation biofuel due to their chemical properties and compatibility with existing infrastructure. It has recently been shown that expression of a bacterial acyl‐transferase in the established industrial workhorse Saccharomyces cerevisiae can lead to production of FAEEs by condensation of fatty acyl‐CoAs and ethanol. In contrast to recent strategies to produce FAEEs in S. cerevisiae through manipulation of de novo fatty acid biosynthesis or a series of arduous genetic manipulations, we introduced a novel genetic background, which is comparable in titer to previous reports with a fraction of the genetic disruption by aiming at increasing the fatty acyl‐CoA pools. In addition, we combined metabolic engineering with modification of culture conditions to produce a maximum titer of over 25 mg/L FAEEs, a 40% improvement over previous reports and a 17‐fold improvement over our initial characterizations. Biotechnol. Bioeng. 2014;111: 2200–2208. © 2014 Wiley Periodicals, Inc. A novel approach for increasing production of fatty acid ethyl esters, an ideal biodiesel, in Saccharomyces cerevisiae is presented. Thompson and Trinh combine rational metabolic engineering to block downstream substrate consuming pathways with more optimal culture conditions designed to increase lipid accumulation to obtain a high level of fatty acid ethyl ester production.