Microbial production of odd‐chain fatty acids

Odd‐chain fatty acids (OcFAs) and their derivatives have attracted much attention due to their beneficial physiological effects and their potential to be alternatives to advanced fuels. However, cells naturally produce even‐chain fatty acids (EcFAs) with negligible OcFAs. In the process of biosynthesis of fatty acids (FAs), the acetyl‐CoA serves as the starter unit for EcFAs, and propionyl‐CoA works as the starter unit for OcFAs. The lack of sufficient propionyl‐CoA, the precursor, is usually regarded as the main restriction for large‐scale bioproduction of OcFAs. In recent years, synthetic biology strategies have been used to modify several microorganisms to produce more propionyl‐CoA that would enable an efficient biosynthesis of OcFAs. This review discusses several reported and potential metabolic pathways for propionyl‐CoA biosynthesis, followed by advances in engineering several cell factories for OcFAs production. Finally, trends and challenges of synthetic biology driven OcFAs production are discussed. Odd‐chain fatty acids (OcFAs) and their derivatives are attractive bioproducts due to their beneficial physiological effects and their potential as advanced fuels. However, cells barely produce OcFAs naturally. Recently, researchers developed different strategies to produce propionyl‐CoA that would enable an efficient biosynthesis of OcFAs. Here, we consider several reported and potential metabolic pathways for propionyl‐CoA, followed by advances in engineering several cell factories for OcFAs production. Finally, trends and key challenges of synthetic biology driven OcFAs production are discussed.