Lipoxygenase Biochemistry in Fatty Acid Metabolism

Lipoxygenases constitute a family of non-heme iron or manganese-dependent enzymes that catalyse the regio- and stereospecific dioxygenation of polyunsaturated fatty acids (PUFAs) to yield hydroperoxy and subsequent oxygenated derivatives. These reactions represent the initial and often rate-limiting steps in the biosynthesis of a diverse array of signalling molecules collectively termed oxylipins. In animals, plant and microbial systems, lipoxygenase-catalysed transformation of linoleic, α-linolenic and arachidonic acids generates bioactive products such as hydroperoxyeicosatetraenoic acids and hydroxyoctadecadienoic acids, which modulate inflammation, cell proliferation, lipid signalling and host–microbe interactions. The catalytic mechanism typically involves hydrogen abstraction at a bis-allylic position, followed by stereospecific oxygen insertion, yielding hydroperoxides that may undergo enzymatic or non-enzymatic conversion to epoxides, diols, leukotrienes and resolvins. Recent advances have elucidated structural determinants of substrate orientation, the impact of membrane-binding domains on enzyme specificity and the diversity of lipoxygenase isoforms across kingdoms. Understanding lipoxygenase biochemistry is central to exploiting these enzymes in biotechnology, agriculture and therapeutic development.

Research from Nature Portfolio

Recent studies have unveiled microbial production of hepoxilins and trioxilins by heterologous expression of bacterial lipoxygenases and epoxide hydrolases, achieving efficient biotransformation of arachidonic, eicosapentaenoic and docosahexaenoic acids into physiologically relevant lipid mediators. Expression of native and engineered 12-LOX and 11-LOX enzymes in Escherichia coli has enabled preparative-scale conversion with yields exceeding 35% for hepoxilins and 10% for trioxilins. Characterisation of peroxisome proliferator-activated receptor-γ partial agonists among these compounds has opened new avenues for lipid-mediator-based drug discovery and mechanistic exploration of inflammation and metabolic regulation.

Lipoxygenase Biochemistry in Fatty Acid Metabolism publication trend

The graph below shows the total number of articles in lipoxygenase biochemistry in fatty acid metabolism across all publications each year (not limited to Nature Index journals).

Technical terms

Lipoxygenase (LOX): An enzyme that introduces dioxygen at specific carbon positions of PUFAs, forming hydroperoxy fatty acids via a non-heme metal cofactor.

Polyunsaturated fatty acids (PUFAs): Fatty acids containing multiple carbon–carbon double bonds, serving as substrates for lipoxygenase and precursors to signalling lipids.

Oxylipins: Oxygenated lipid mediators derived from PUFAs through lipoxygenase and related pathways, involved in physiological regulation and stress responses.

Hydroperoxide: The immediate product of PUFA dioxygenation by lipoxygenase, bearing a –OOH group that is converted into downstream signalling molecules.

Regioselectivity: The enzyme’s preference for oxygenation at a specific carbon atom of the fatty acid substrate, determining the structural isomer of the product.

References

1. Production of recombinant intact and N-terminal truncated lipoxygenase isozyme III expressed in Saccharomyces cerevisiae and its influence on glutenin polypeptides. Food Chemistry Molecular Sciences (2024).
2. Discovery of α-Linolenic Acid 16(S)-Lipoxygenase: Cucumber (Cucumis sativus L.) Vegetative Lipoxygenase 3. International Journal of Molecular Sciences (2023).
3. Biotransformation of polyunsaturated fatty acids to bioactive hepoxilins and trioxilins by microbial enzymes. Nature Communications (2018).
4. Bacterial lipoxygenases: Biochemical characteristics, molecular structure and potential applications. Biotechnology Advances (2022).