期刊
出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2201711119
关键词
metabolic engineering; methylotrophic yeast; synthetic biotechnology; oleochemicals; biofuels
资金
- National Natural Science Foundation of China [21922812, 22161142008]
- National Key Research and Development Program of China [2021YFC2103500]
- DICP innovation grant from Dalian Institute of Chemicals Physics, CAS [DICP I201920, I202111]
Methanol-based biorefinery is a promising strategy for achieving carbon neutrality goals. This study successfully rewired the global metabolism of Pichia pastoris to efficiently produce free fatty acids and fatty alcohols from methanol.
Methanol-based biorefinery is a promising strategy to achieve carbon neutrality goals by linking CO2 capture and solar energy storage. As a typical methylotroph, Pichia pastoris shows great potential in methanol biotransformation. However, challenges still remain in engineering methanol metabolism for chemical overproduction. Here, we present the global rewiring of the central metabolism for efficient production of free fatty acids (FFAs; 23.4 g/L) from methanol, with an enhanced supply of precursors and cofactors, as well as decreased accumulation of formaldehyde. Finally, metabolic transforming of the fatty acid cell factory enabled overproduction of fatty alcohols (2.0 g/L) from methanol. This study demonstrated that global metabolic rewiring released the great potential of P. pastoris for methanol biotransformation toward chemical overproduction.
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