Technology
Researchers at Goethe University Frankfurt have developed a biotechnology platform for the precise and sustainable production of short- and medium-chain fatty acids (C6-C16) through protein engineering of fatty acid synthase FAS. The platform provides a viable alternative to conventional sources such as palm oil or coconut oil extraction and enables the production of tailored precursors for food, cosmetics and industrial applications.
Natural fatty acid synthesis is intrinsically biased toward longer-chain products, which limits access to short- and medium-chain fatty acids that are highly relevant for industrial and consumer applications. Through targeted molecular engineering and yeast-based production, the Designer-FAS platform overcomes this natural C16 chain-length constraint and enables tailored fatty acid production at industrially relevant titers.
The platform is based on the engineering of fatty acid synthase to control chain length and product release with high specificity. Strategic modifications in the ketoacyl synthase domain alter the substrate-binding pocket and elongation efficiency, while replacement of the mammalian termination domain with bacterial ‘TesA broadens substrate acceptance across the C8-C18 range.
An alternative pathway integrates thioreductase domains to enable direct production of fatty aldehydes and fatty alcohols instead of free fatty acids. Systematic combination of KS and TE/TR variants generated a focused library of designer FAS variants spanning distinct product profiles with high specificity.
The engineered systems have been successfully implemented in industrial yeast platforms, including Ogataea polymorpha. In shake-flask cultivation, the platform achieved 90.8 mg/L medium-chain fatty acids, corresponding to 83 percent of total free fatty acids, while fed-batch fermentation reached 674–708.6 mg/L depending on strain and conditions.
