Biocatalyst-driven synthesis of essential industrial chemicals

The Campopiano Group, with industrial collaborators Ingenza, a spin out from the School of Chemistry, are advancing their breakthrough biocatalytic route for the sustainable production of Guerbet lipids towards commercial viability.

In brief:

  • Industrial biotechnology aims to produce commodity and high value chemicals, as well as bioactives such as proteins and antibodies, through greener bio-based methods, and will play an important role in the transition to more sustainable industrial production.

  • The development of industrial biotechnology relies on molecular understanding of the enzymes that catalyse biosynthetic pathways, allowing these to be re-purposed as biocatalysts enabling the synthesis of target molecules in a sustainable way.

  • The Campopiano Group carries out innovative research at the intersection of synthetic chemistry, protein chemistry, and microbiology, unravelling the structure, function and mechanism of the biosynthesis of natural products, and enhancing enzyme function towards applications in biotechnology, medicine, and sustainability in chemical production.​

  • In collaboration with industrial partners Ingenza, the group identified a biocatalytic cascade able to convert simple, low-value fatty acids to Guerbet lipids, a valuable commodity chemical still produced with expensive metal catalysts via energy-intensive chemical conditions that haven’t changed since 1899. 

  • Continuing collaboration is optimising the process towards commercial viability, using BBSRC IAA funding to identify compatible biocatalysts that will enable the synthetic route to be scaled up and incorporated into a suitable microbial host.

Read more below.

Graphical abstract of synthesis process

The challenge: Finding sustainable replacements for essential industrial catalysts

Enzymes are Nature’s remarkable natural catalysts found in every living organism. Used as biocatalysts, they provide an attractive, environmentally friendly alternative to conventional chemical catalysts, and are expected to play an essential role in the development of sustainable industrial processes that maximise resource utilization and minimise waste. Biocatalysis opens up the use of cheaper and bio-based raw materials, including re-use of waste streams, and can shorten chemical process routes – both vital routes to enhanced sustainability and reduced greenhouse gas emissions. 

A major challenge in the development of biocatalysis, however, is that enzymes tend to be highly specific for a small number of substrates and/or not stable in the conditions used in industrial processes. However, enzyme performance can be improved by a process known as “directed evolution”, a combination of protein engineering (by semi-rational or random mutagenesis) and selective screening of the best variants.

Image of chemiscal plant at sunset
Industrial metalworking

Guerbet lipids are valuable commodity chemicals that are used in industry as lubricants in applications including cosmetics, pharmaceuticals, metalworking, and for the production of specialty chemicals. In their “traditional” chemical synthesis they are prepared from fossil fuels using harsh, energy-intensive chemical conditions (high temperatures and pressure) and expensive metal catalysts such as Raney Nickel or Ruthenium – a process that has not been innovated upon since its invention by Marcel Guerbet himself in 1899. The market for Guerbet lipids faces emerging challenges such as production and energy costs, as well as more stringent environmental regulations. Biocatalysis might offer a solution, but no bio-based production process has yet been put forward.

The chemistry solution: Molecular understanding to underpin industrial biotechnology

For over 27 years, the School of Chemistry’s Professor Dominic Campopiano and his group have been studying the structure, function and mechanism of the biosynthesis of natural products such as lipids, vitamins, and antibiotics. Key to this is a molecular understanding of the enzymes that catalyse the steps in these pathways, allowing these to be re-purposed as biocatalysts enabling the synthesis of target molecules in a sustainable way. If the natural enzyme does not function in the desired way, the team employs advanced techniques, including directed evolution and high-throughput screening, to enhance enzyme activity and stability. Desirable biocatalyst properties such as substrate selectivity and tolerance of organic solvents can also be selected. Furthermore, these biocatalysts can be put together in efficient cascades that can build complex molecules from simple precursors in sequentially-linked steps.

The Campopiano Group operates two primary laboratories: a chemistry lab and a biology lab, both equipped with state-of-the-art technology. This, in combination with the advanced NMR and mass spectrometry facilities provided by the School of Chemistry, gives the group advanced research capabilities that allow them to push the boundaries of interdisciplinary science at the intersection of synthetic chemistry, protein chemistry, and microbiology.

Partnering towards a sustainable commercial solution: Collaboration with Ingenza 

Ingenza is a world-leading engineering biology and industrial biotechnology company which provides contract research, development and manufacturing services in applied biosciences to produce a variety of commercial bio-based targets for the chemical, polymer, energy and pharma industries. Over many years, multiple strands of ongoing collaboration with School of Chemistry researchers have uncovered new chemistry and led to potential new processes for the company. 

Ingenza logo

Collaboration between the Campopiano Group and Ingenza to develop bio-based routes to Guerbert lipid production started in 2017 with funding from the Industrial Biotechnology Innovation Centre (IBioIC) for a 1-year Proof of Concept study. A four-year PhD studentship funded by BBSRC and IBioIC then successfully developed a biocatalytic cascade able to convert simple, low-value fatty acids to Guerbet lipids, resulting in a breakthrough 2024 paper published in ACS Catalysis (Herrera et al, 2024).

To progress their new biocatalytic route towards commercial viability, the team have now identified two new biocatalysts that will improve efficiency and enable the turnover towards various Guerbet lipid derivatives, including alcohols, as well as acids. Funding secured from the BBSRC Impact Acceleration Account (IAA) will enable them to develop a combined biocatalytic cascade that will increase the overall % conversion from simple fatty acids. Successful demonstration of an optimised process to convert low value fatty acids (potentially from lipid-rich waste streams such as food waste, animal fats and cooking oils) into high-value Guerbet products will open up the prospect of a greener route towards these important industrially-relevant chemicals, with potential to integrate into the circular bioeconomy.

The Campopiano Group hosts a range of undergraduate student projects, both BSc Hons and MChem students, as well as hosting recent visitors from Chicago and Groningen. PhD students often work in collaboration with industrial partners such as Ingenza, Johnson Matthey and Syngenta. Members from the group often team up with other SoC PIs in synthetic organic chemistry and analytical chemistry. They also develop long term collaborations with experts in the USA, Europe and China.

In 2024, one Campopiano group publication in the Royal Society of Chemistry Faraday Discussions was unique in being co-authored by a team of ten School of Chemistry undergraduate and postgraduate taught Masters students alongside the PhD students and postdoctoral research assistants who supervised their work in the lab (and SoC colleagues Prof. Alison Hulme and Dr Annamaria Lilienkampf). The undergraduate students carried out this project as part of their Chem4P lab course (a laboratory-based research training course in preparation for the final year project) and summer internships (Kennedy et al, 2024).

Read more:

School of Chemistry students publish in Faraday Discussion on Biocatalysis

https://chem.ed.ac.uk/school-chemistry-students-publish-faraday-discussion-biocatalysis 


More widely, the Campopiano group combines synthetic chemistry, protein chemistry, and microbiology to study important proteins, enzymes, and natural products from both mammals and bacteria. One particular focus over the last ~20 years has been an understanding of how mammals and bacteria make sphingolipids and ceramides, essential membrane components and key elements of the microbiome (Stankeviciute et al, 2022). They specialize in cloning and over-expressing target genes to prepare the recombinant proteins they encode, and use advanced techniques to analyse their 3D structures and catalytic mechanisms such as AlphaFold and ligand docking methods. Their work advances knowledge in biochemistry and its applications in biotechnology, medicine, and sustainability in chemical production (Ashley et al, 2025).​

Campopiano group website


Herrera et al, Campopiano. Repurposing a Fully Reducing Polyketide Synthase toward 2-Methyl Guerbet-like Lipids. ACS Catalysis (2024), doi.org/10.1021/acscatal.4c04714.

Kennedy et al, Campopiano. Developing deprotectase biocatalysts for synthesis. Faraday Discussion, (2024), 252, 174-187. doi: 10.1039/D4FD00016A.

Stankeviciute et al., Campopiano Convergent evolution of bacterial ceramide synthesis. Nature Chem. Biol. (2022) 18, 305–312. doi.org/10.1038/s41589-021-00948-7.

Ashley, B., Mathew, S., Sajjad, M. et al. Campopiano. Rational engineering of a thermostable α-oxoamine synthase biocatalyst expands the substrate scope and synthetic applicability. Commun. Chem. (2025) 8, 78. doi.org/10.1038/s42004-025-01448-8.


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