Microbial Fermentation for Platform Chemical Production

Microbial fermentation harnesses the catalytic power of microorganisms to convert renewable substrates into platform chemicals—key intermediates for fuels, polymers and fine chemicals. Advances in systems biology and synthetic biology have enabled precise rewiring of metabolic pathways to boost yields, levels of purity and substrate versatility. Common targets include 2,3-butanediol, acetoin, succinic acid and lactic acid, which can be derived from sugars, agro-industrial residues or glycerol by tailored strains of yeast and bacteria. Modern process development integrates fed-batch or continuous bioreactor schemes with in situ cofactor regeneration, redox balancing and product separation technologies. Life cycle assessments now guide optimisation of energy use and greenhouse gas emissions, ensuring alignment with circular economy principles. This multidisciplinary field has seen rapid scale-up from laboratory proof of concept to industrial demonstration, underscoring its global significance in reducing reliance on petrochemicals and valorising waste streams.

Research from Nature Portfolio

Recent studies have demonstrated high-titer acetoin production in engineered Saccharomyces cerevisiae by eliminating ethanol and glycerol pathways and introducing an NADH oxidase system to regenerate NAD+, achieving over 100 g/L acetoin with yields near 0.44 g/g glucose. In a complementary investigation, Lactococcus lactis was reprogrammed to funnel lactose-derived carbon into (3R)-acetoin and two butanediol stereoisomers, attaining titres of 27 g/L acetoin, 51 g/L meso-2,3-butanediol and 32 g/L (2R,3R)-butanediol from dairy waste with enantiomeric purities exceeding 80 % of theoretical yield.

Microbial Fermentation for Platform Chemical Production publication trend

The graph below shows the total number of articles in microbial fermentation for platform chemical production across all publications each year (not limited to Nature Index journals).

Technical terms

Platform chemical: A basic molecular building block for synthesising a variety of higher-value chemicals.

Metabolic engineering: Rational alteration of cellular metabolism to increase flux towards desired products.

Fed-batch fermentation: A cultivation strategy where substrates are progressively fed to a bioreactor to sustain microbial growth and product formation.

NAD+ regeneration: The enzymatic recycling of nicotinamide adenine dinucleotide to maintain redox balance during biosynthesis.

Chiral purity: The predominance of one enantiomer over another in an optically active compound, affecting its functional properties.

References

1. Efficient production of acetoin in Saccharomyces cerevisiae by disruption of 2,3-butanediol dehydrogenase and expression of NADH oxidase. Scientific Reports (2016).
2. Synthesis of (3R)-acetoin and 2,3-butanediol isomers by metabolically engineered Lactococcus lactis. Scientific Reports (2016).
3. Life Cycle Assessment of Microbial 2,3-Butanediol Production from Brewer’s Spent Grain Modeled on Pinch Technology. ACS Sustainable Chemistry & Engineering (2023).
4. High production of 2,3-butanediol from biodiesel-derived crude glycerol by metabolically engineered Klebsiella oxytoca M1. Biotechnology for Biofuels and Bioproducts (2015).