Many petroleum-derived chemicals can be directly or functionally substituted with chemicals produced from renewable feedstocks. Among these compounds, short chain fatty acids and other polyketides can fulfill a role as platform molecules using their functional group as a target for chemical catalysis. The native Saccharomyces cerevisiae fatty acid synthase (FAS) is not amenable to manipulation to produce shorter chain fatty acids. Therefore, we have introduced heterologous fatty acid synthases (human type I FAS and bacterial type II FAS), phosphopantetheine transferases, and the appropriate thioesterases for the desired product length. Enzyme engineering and initial strain engineering increased titers of short chain fatty acids more than 60-fold. Subsequent pathway engineering has been used to prevent fatty acid degradation, to control product sequestration, and to increase the required precursor pools. These efforts have substantially improved the titers of short or medium chain fatty acids. Our results also demonstrate the advantages of balancing native and non-native pathways in the yeast to enhance its performance as a biocatalyst. The strategies employed will prove useful for other polyketide products.

Engineering <i>Saccharomyces cerevisiae</i> as a biocatalyst for the synthesis of short and medium chain fatty acids

247th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.

Engineering Saccharomyces cerevisiae as a biocatalyst for the synthesis of short and medium chain fatty acids