Polyketide synthase–like functionality acquired by plant fatty acid elongase

Vegetable oils serve as critical feedstocks for biofuels and bioproducts by providing energy-dense hydrocarbon molecules. Some plants have evolved divergent enzyme sets to produce high-value "unusual fatty acids" with novel chain lengths or functional groups. A new study by researchers at the Center for Advanced Bioenergy and Bioproducts Innovation (CABBI) aims to elucidate and harness an unusual fatty acid biosynthetic pathway in seeds of Orychophragmus limprichtianus to expand the synthetic biology toolbox for plant/microbe-based bioproducts.

Researchers conducted advanced lipid analysis utilizing TLC, GC-MS, and LC-MS to identify and characterize the previously unknown fatty acid composition in seeds of O. limprichtianus. They combined biochemical assays and molecular biology with AI-guided protein structure modeling to better understand the molecular mechanism of biosynthetic pathway. The proposed biosynthetic pathway was reconstructed in an engineered oilseed host to validate enzyme functionalities in vivo.

Unusual fatty acids in O. limprichtianus seeds were identified as C₂₄-C₂₈ keto-hydroxy fatty acids. This distinct lipid profile is driven by two divergent enzymes: a fatty acid elongase 1 (FAE1) and a 3-ketoacyl-CoA reductase (KCR1). This revealed a biosynthetic pathway where the plant system acquires a bacterial polyketide synthase (PKS)-like discontinuous elongation functionality.

This work reveals unprecedented evolutionary plasticity in plant lipid metabolism, breaking traditional boundaries of fatty acid engineering. The researchers successfully reconstructed this pathway in an engineered oilseed host, establishing a powerful synthetic biology toolkit to produce high-value oil. This work provides a scalable bio-based source for industrial lubricants, which can support the bioeconomy.

This work was funded by CABBI, a U.S. Department of Energy-funded Bioenergy Research Center, with a grant from the DOE Office of Science, Biological and Environmental Research Program.

Images available upon request.