Spinning Green: Lipase-Catalyzed Synthesis of Bioactive Fatty Acid Amides from Renewable Lipid Feedstocks in a Rotating Bed Reactor

Fatty acid ethanolamides (FAEAs) are bioactive lipids involved in inflammation, pain modulation, and energy homeostasis, gaining interest in the pharmaceutical, nutraceutical, and cosmetic sectors. Here, we present an intensified biocatalytic strategy for the synthesis of a mixture of FAEAspalmitoylethanolamide (PEA), oleoylethanolamide (OLA), stearoylethanolamide (SEA), and linoleoylethanolamide (LEA)starting from microbial lipids extracted from<i>Cutaneotrichosporon oleaginosus</i>, cultivated on whey permeate, a major dairy byproduct, supplemented with waste cooking oil. The two-step enzymatic cascadetransesterification of triacylglycerols into ethyl esters followed by aminolysis with ethanolaminewas catalyzed by Novozym 435 (immobilized <i>Candida antarctica</i> lipase B) in green solvents. Whereas ethanol has been used for the first step, eucalyptol proved particularly effective in aminolysis reaction with >99% conversion and complete selectivity. Process intensification <i>via</i> a SpinChem rotating bed reactor led to a 5-fold reduction in reaction time (48 to 10 h), a 5- to 7-times increase in space-time yield and quantitative yields for both steps. Biocatalyst reusability and process reproducibility was preserved. This integrated platform exemplifies a circular bioeconomy approach by valorizing agri-industrial residues into high-value compounds through clean and scalable technologies. The resulting FAEAs hold potential for synergistic therapeutic applications, while supporting cost-effective and sustainable manufacturing across diverse industries.