Methanol is an ideal feedstock for bio-manufacturing. Converting it into lactate, a monomer for biodegradable plastic, offers a promising strategy for addressing the challenge of white pollution. However, it remains difficult to engineer microbes to produce lactate from methanol due to methanol toxicity and strong competition between product synthesis and cell growth.

In a study published in Nature Communications, a team led by Prof. ZHOU Yongjin from the Dalian Institute of Chemical Physics of the Chinese Academy of Sciences, along with Prof. FEI Qiang from Xi'an Jiaotong University, developed a yeast cell factory to produce L-lactate from methanol as the sole carbon source, and evaluated the commercial potential and environmental impacts of this bioprocess.

Researchers extensively rewired the metabolism of the yeast Ogataea polymorpha to enable overproduction of L-lactate from methanol, and discovered a distinct cofactor distribution pattern in methanol metabolism. Based on this cofactor regulation mechanism, they developed cofactor engineering and mitochondrial compartmentalization strategies, substantially enhancing L-lactate biosynthesis.

Through techno-economic analysis and life cycle assessment, researchers showed that the minimum selling price of L-lactate produced from methanol was 2.29 dollar/kg with the annual capacity of 18,500 tons. They also showed that the synthesis of 1 ton of L-lactate resulted in a carbon deposition of 7.29 tons, realizing the carbon-negative production. These demonstrate the economic and environmental value of producing CO₂-derived L-lactate by coupling chemical and biological catalysis. 

"Our work not only paves the way for engineering methanol metabolism to produce lactate, but also shows a broader vision for a circular economy by establishing a direct link between biodegradable plastics and carbon neutrality," said Prof. ZHOU.