Elevated acetyl‐CoA by amino acid recycling fuels microalgal neutral lipid accumulation in exponential growth phase for biofuel production
Lina Yaoa b, Hui Shena b, Nan Wangc d, Jaspaul Tatlayc d, Liang Lic d, Tin Wee Tane f g h, Yuan Kun Leea b✉
- aDepartment of Microbiology and Immunology Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore
- bDepartment of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- cDepartment of Chemistry University of Alberta Edmonton Alberta Canada
- dDepartment of Chemistry, University of Alberta, Edmonton, Alberta, Canada
- eDepartment of Biochemistry Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore
- fNational Supercomputing Centre (NSCC) Singapore Singapore
- gDepartment of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- hNational Supercomputing Centre (NSCC), Singapore, Singapore
- ✉Corresponding author
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Abstract
Microalgal neutral lipids [mainly in the form of triacylglycerols (TAGs)], feasible substrates for biofuel, are typically accumulated during the stationary growth phase. To make microalgal biofuels economically competitive with fossil fuels, generating strains that trigger TAG accumulation from the exponential growth phase is a promising biological approach. The regulatory mechanisms to trigger TAG accumulation from the exponential growth phase (TAEP) are important to be uncovered for advancing economic feasibility. Through the inhibition of pyruvate dehydrogenase kinase by sodium dichloroacetate, acetyl-CoA level increased, resulting in TAEP in microalga Dunaliella tertiolecta. We further reported refilling of acetyl-CoA pool through branched-chain amino acid catabolism contributed to an overall sixfold TAEP with marginal compromise (4%) on growth in a TAG-rich D. tertiolecta mutant from targeted screening. Herein, a three-step α loop-integrated metabolic model is introduced to shed lights on the neutral lipid regulatory mechanism. This article provides novel approaches to compress lipid production phase and heightens lipid productivity and photosynthetic carbon capture via enhancing acetyl-CoA level, which would optimize renewable microalgal biofuel to fulfil the demanding fuel market.

