Engineering the methylotrophic yeast Ogataea polymorpha for lactate production from methanol

Area of Science:

• Biotechnology and Industrial Microbiology
• Synthetic Biology
• Sustainable Chemistry

Background:

• Lactate is a key platform chemical for bioplastics like poly-lactic acid (PLA).
• Current production relies on sugars, prompting research into sustainable, non-food feedstocks.
• Methanol, derived from CO2, presents a promising alternative carbon source.

Purpose of the Study:

• To engineer the methylotrophic yeast Ogataea polymorpha for lactate production from methanol.
• To optimize fermentation conditions and enhance methanol assimilation for improved lactate titers.
• To establish a proof-of-principle for utilizing CO2-derived substrates in industrial biotechnology.

Main Methods:

• Expression of four different lactate dehydrogenases in Ogataea polymorpha under methanol-inducible promoter.
• Optimization of fed-batch fermentation with varying nitrogen sources and pH control.
• Adaptive laboratory evolution to enhance methanol assimilation in engineered strains.

Main Results:

• Successful expression and function of Lactobacillus helveticus L-lactate dehydrogenase in Ogataea polymorpha.
• Engineered strain exhibited a 55% increase in growth rate on methanol while maintaining lactate production.
• A maximum lactate titer of 3.8 g/L was achieved using an evolved strain in fed-batch culture with urea.

Conclusions:

• Ogataea polymorpha is a viable host for producing lactate from methanol.
• The study provides a foundation for engineering methylotrophic organisms for CO2-based chemical production.
• This approach supports sustainable industrial biotechnology with reduced land use.