Metabolic Engineering of Oleaginous Microorganisms

Oleaginous microorganisms, including certain yeasts, algae and filamentous fungi, have the intrinsic capacity to accumulate lipids to levels exceeding 20 percent of their cellular dry weight. Metabolic engineering seeks to redirect carbon flux towards fatty acid synthesis and storage by rewiring native pathways, enhancing precursor availability, and modifying regulatory circuits. Central strategies include amplification of key enzymes such as acetyl-CoA carboxylase, engineering of subcellular compartments to concentrate intermediates, and optimisation of redox cofactors. Selection of robust host strains, whether naturally oleaginous or engineered from model organisms, is complemented by tailor-made promoters and genome editing tools to achieve high titres of triacylglycerols, free fatty acids or derived oleochemicals. Feedstock flexibility is pursued through valorisation of low-cost substrates such as lignocellulosic hydrolysates, crude glycerol or industrial wastes. Advances in synthetic biology modules—ranging from regulatory sensors to dynamic control circuits—have enabled strains that balance growth with product formation and that perform in large-scale bioreactors. The global significance of this research lies in its potential to supply sustainable biofuels, bioplastics, nutraceuticals and specialty chemicals, reducing reliance on fossil resources and contributing to a circular bioeconomy.

Research from Nature Portfolio

Recent studies have demonstrated the power of chassis refinement and pathway integration to transform conventional yeasts into efficient lipid or complex-molecule producers. One approach introduced precise genome modifications to create an open-access chassis strain that combines enhanced transformability with improved protein secretion, thereby laying a foundation for rapid installation of lipid-producing pathways. In parallel, de novo biosynthesis of a pharmaceutically and flavour-active flavonoid was achieved by systematically balancing parallel biosynthetic routes in Saccharomyces cerevisiae, employing enzyme fusions, precursor-supply engineering and peroxisomal compartmentalisation to boost metabolite titres by orders of magnitude. Foundational work in a model yeast cell factory has also reported the highest recorded accumulation of free fatty acids in Saccharomyces cerevisiae, along with downstream conversion into alkanes and fatty alcohols, illustrating how iterative enzyme screening and strain optimisation can yield platform strains for diverse oleochemical products.

Metabolic Engineering of Oleaginous Microorganisms publication trend

The graph below shows the total number of articles in metabolic engineering of oleaginous microorganisms across all publications each year (not limited to Nature Index journals).

Technical terms

Oleaginous microorganisms: Microbes capable of accumulating lipids above 20 percent of their biomass.

Metabolic engineering: Deliberate modification of metabolic pathways to increase yield, productivity or versatility of target compounds.

Acetyl-CoA: A central metabolite serving as the two-carbon donor for fatty acid biosynthesis.

Peroxisomal engineering: Targeting and optimisation of enzymatic steps within peroxisomes to enhance specific metabolic fluxes.

Feedstock valorisation: Conversion of low-value or waste substrates into high-value chemicals or fuels.

References

1. OPENPichia: licence-free Komagataella phaffii chassis strains and toolkit for protein expression. Nature Microbiology (2024).
2. De novo biosynthesis of the hops bioactive flavonoid xanthohumol in yeast. Nature Communications (2024).
3. Production of fatty acid-derived oleochemicals and biofuels by synthetic yeast cell factories. Nature Communications (2016).
4. Sustainable valorization of waste glycerol into bioethanol and biodiesel through biocircular approaches: a review. Environmental Chemistry Letters (2023).
5. Systematic sequence engineering enhances the induction strength of the glucose-regulated GTH1 promoter of Komagataella phaffii. Nucleic Acids Research (2023).
6. Combinatorial optimization of CRISPR/Cas9 expression enables precision genome engineering in the methylotrophic yeast Pichia pastoris. Journal of Biotechnology (2016).