Ideal Genetic “Recipe” for Producing D-Lactic Acid Discovered

Great recipes require the perfect combination of ingredients — biotechnology recipes are no exception.

Researchers from Osaka Metropolitan University have discovered the ideal genetic “recipe” to turn yeast into a tiny yet powerful eco-friendly factory that converts methanol into D-lactic acid, a key compound used in biodegradable plastics and pharmaceuticals. This approach could help reduce reliance on petroleum-based processes and contribute to more sustainable chemical production.

Lactic acid is widely used in food, cosmetics, pharmaceuticals and bioplastics. It exists in two forms: L-lactic acid and D-lactic acid. Compared to its counterpart, D-lactic acid is much less available and much more expensive.

“Most lactic acid bacteria can only produce L-lactic acid whilst chemical synthesis methods yield only a mixture of both forms,” said Ryosuke Yamada, an associate professor at Osaka Metropolitan University’s Graduate School of Engineering and lead author of this study.

Seeking a more efficient way to produce D-lactic acid, the team turned to Komagataella phaffii, a yeast capable of utilizing methanol. Their goal was to pinpoint the optimal combination of D-lactate dehydrogenase (D-LDH) genes and promoters in K. phaffii that would maximize the yeast’s ability to produce D-lactic acid from methanol. D-LDH is a key enzyme responsible for converting precursor molecules into D-lactic acid, while promoters are DNA sequences that regulate gene expression.

After testing five different D-LDH genes and eight promoters, the researchers identified an ideal mix that boosted D-lactic acid production by 1.5 times compared to other methanol-based methods.

“To the best of our knowledge, our engineered yeast achieved the highest-ever reported yield using methanol as the sole carbon source,” Yamada said.

These findings show that engineered yeast strains can be tailored to produce a wide range of useful compounds for commercial use. With growing global concerns over fossil fuel depletion and environmental impact, the ability to synthesize chemicals from renewable carbon sources like methanol is deemed a critical advancement for sustainability.

“This study demonstrates that by carefully optimizing gene and promoter combinations, we can significantly enhance the efficiency of microbial processes, offering a viable alternative to traditional, petroleum-based chemical production,” Yamada said.

Reference: Inoue Y, Yamada R, Matsumoto T, Ogino H. Enhancing D-lactic acid production by optimizing the expression of D-LDH gene in methylotrophic yeast Komagataella phaffii. Biotechnol Biofuels. 2024;17(1):149. doi: 10.1186/s13068-024-02596-0

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