Using methanol yeasts such as Pichia pastors or Hansenula as a cellular catalyst, researchers at the CAS Dalian Institute of Chemical Physics have achieved efficient synthesis of fatty acid derivatives from methanol bioconversion by combining adaptive evolution and rational metabolic engineering modification.
The researchers found that the engineered strain could not grow in methanol during the modification of endogenous metabolism for fatty acid synthesis with polymorphic Hansenula as the host. The domesticated strain, obtained through adaptive laboratory evolution, was able to grow normally in methanol and produce fatty acids efficiently. They rearranged the global intracellular metabolism and enhanced the supply of precursor acetyl coenzyme A and cofactor NADPH, allowing Hansenula to synthesize fatty acids using methanol as the only carbon source with a yield of 15.9 g/L.
In Baker’s yeast, the accumulation of formaldehyde affected the efficiency of methanol biotransformation; by optimizing the process of cell-centered metabolism and cofactor regeneration and enhancing the methanol metabolic pathway, the team significantly reduced formaldehyde accumulation and increased fatty acid yield (23.4 g/L). They also used a metabolic switching strategy to rapidly transform the fatty acid-producing strain into a fatty alcohol cell factory, simplifying the strain construction process and enabling a fatty alcohol yield of 2.0 g/L.