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L2503

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

Martina Bigliardi, Silvia Donzella, Diana-Ionela Dăescu, Alessandro Pellis, Lucia Tamborini, Andrea Pinto, and Martina L. Contente

ACS Sustainable Chem. Eng., 2025, 13, pp. 18214-18222.

Source:

"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 Cutaneotrichosporon oleaginosus, 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 Candida antarctica 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 via 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."

Short Summary / Highlights:

  • 5-fold faster reactions: SpinChem RBR reduced reaction time from 48h to just 10h for the complete two-step cascade
  • Enhanced productivity: Space-time yield increased 5-7 times compared to conventional batch processes (transesterification: 1.3 to 7.5 g/L/h; aminolysis: 1.3 to 5.3 g/L/h)
  • Excellent catalyst reusability: The immobilized enzyme was reused over five complete cascade cycles with <10% loss in catalytic performance
  • Sustainable process: Used green solvents (ethanol and eucalyptol) and waste feedstocks (whey permeate and waste cooking oil) to produce high-value bioactive compounds
  • Complete selectivity: Achieved >99% conversion and quantitative yields for both enzymatic steps
  • Industrial relevance: "The gentle agitation of the rotating bed reactor minimizing mechanical stress on the enzyme, enabling its reuse over five cascade cycles... with <10% loss in catalytic performance"

 

L2503 Schematic representation of the intensified process in SpinChem reactor for the lipase-catalyzed synthesis of fatty amides, starting from a TAGs-rich extract and ethanolamine.
Schematic representation of the intensified process in SpinChem reactor for the lipase-catalyzed synthesis of fatty amides, starting from a TAGs-rich extract and ethanolamine.

 

Authors & Research Group

This research was conducted by a collaborative team from the University of Milan and University of Genoa, Italy:

Principal Investigator:

  • Martina L. Contente (Corresponding Author) - University of Milan, Department of Food, Nutrition and Environmental Sciences (DeFENS). Research focus: Biocatalysis, process intensification, and sustainable bioprocessing.

Research Team:

  • Martina Bigliardi - University of Milan, DeFENS
  • Silvia Donzella - University of Milan, DeFENS. Expertise in oleaginous yeast cultivation and microbial lipid production
  • Diana-Ionela Dăescu - Politehnica University Timișoara (Romania) & University of Genoa (Italy)
  • Alessandro Pellis - University of Genoa, Department of Chemistry and Industrial Chemistry. Focus on green chemistry and biocatalysis
  • Lucia Tamborini - University of Milan, Department of Pharmaceutical Sciences (DISFARM)
  • Andrea Pinto - University of Milan, DeFENS

The group specializes in sustainable biocatalytic processes, waste valorization, and circular bioeconomy approaches, with particular expertise in enzyme-catalyzed synthesis and process intensification technologies.

SpinChem Commentary
Erik Löfgren CTO SpinChem

Erik Löfgren

Chief Technology Officer

erik@spinchem.com

This study from the University of Milan demonstrates exactly why rotating bed reactor technology is becoming the preferred choice for industrial biocatalysis. The researchers faced a common challenge: their lipid feedstock was extremely viscous, making it incompatible with flow systems that would normally be the first choice for continuous processing.

The SpinChem RBR solved three critical problems simultaneously:

Process intensification. The reactor delivered a 5-fold reduction in reaction time, with a 5–7-fold increase in space‑time yield compared to conventional batch processing, directly translating to smaller equipment footprints and higher throughput.

Catalyst lifetime. The immobilized enzyme was reused for five complete two-step cascade cycles with less than 10% loss in performance; a result which is economically favourable. The gentle treatment of the solids protects the biocatalyst from mechanical stress while maintaining fast mass transfer, which is hard to achieve in traditional stirred vessels.

Sustainability of substrates. Starting from dairy waste (whey permeate) and waste cooking oil, the team produced high-value bioactive compounds using only green solvents. The efficiency of the RBR made this sustainable route economically viable, proving that with the right technology environmental responsibility and process economics can align.

For researchers and process engineers working with immobilized enzymes, challenging substrates, or multi-step cascades, this paper provides a validated roadmap: intensified biocatalysis at scale, with catalyst reusability that actually works in practice.

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Industries Pharmaceutical, Food and Beverage

Topics Biocatalysis, Scientific Literature

Products SpinChem® RBR S2