Reprogramming yeast metabolism to Alter fatty acid profiles from even-chain to odd-chain Configuration

Odd-chain fatty acids have significant applications in biofuels and pharmaceutical industries. In this study, a yeast cell factory was engineered to produce odd-chain fatty acids and their derivatives. The threonine biosynthesis pathway was initially engineered to enable the de novo synthesis of odd-chain fatty acids, resulting in odd-chain fatty acids accounting for 24.7 % of the total fatty acids. Subsequently, silencing the native fatty acid synthase and introducing a fatty acid synthase from Rhodotorula toruloides, which exhibits higher affinity for propionyl-CoA than the native enzyme, increased the proportion of odd-chain fatty acids to 51.9 %. Further modifications to the lipid metabolism enabled the production of odd-chain free fatty acids (184.1  mg/L) and odd-chain triglycerides (75.2  mg/g). This study successfully shifted the metabolism of Saccharomyces cerevisiae from traditional even-chain fatty acids to a strain dominant in odd-chain fatty acids, demonstrating the potential to develop a novel platform strain for producing specific odd-chain fatty acids derivatives.