Knockout of the DAS gene increases S-adenosylmethionine production in Komagataella phaffii

Abstract

S-adenosylmethionine (SAM) is an important compound in living organisms and has a number of different roles, such as polyamine synthesis. It can also be used for the treatment of diseases. Gene targeting with homologous recombination in Komagataella phaffii (K. phaffii) created DAS1 and DAS2 gene knockout strains, which use the methanol pathway to generate more ATP and increase SAM production. These strains showed an increase in the flux of methanol oxidation and an increase in ATP production. The gene knockout retarded the cell growth in the late phase of induction, did not influence the total methanol consumption or the activity of SAM synthetase, but did significantly increase the yield of SAM by 43.7%. The metabolic flux of methanol oxidation is increased by DAS1 and DAS2 gene knockout, which leads to an increase in ATP and higher SAM production.

Keywords:

• Komagataella phaffii (Pichia pastoris)
• S-adenosylmethionine (SAM)
• dihydroxyacetone synthase (DAS)
• ATP

Acknowledgment

This work was supported by the National Natural Science Foundation of China (No. 31870045).

Disclosure statement

All authors declare they have no other competing interests.