title: Elevated acetyl-CoA by amino acid recycling fuels microalgal neutral lipid accumulation in exponential growth phase for biofuel production.
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.
authors.affiliation: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Lina
authors.initials: L
authors.lastname: Yao
authors.affiliation: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Jaspaul
authors.initials: J
authors.lastname: Tatlay
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.|National Supercomputing Centre (NSCC), Singapore, Singapore.
authors.forename: Tin Wee
authors.initials: TW
authors.lastname: Tan
authors.affiliation: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Yuan Kun
authors.initials: YK
authors.lastname: Lee
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism*; D056804:Biofuels; D058086:Microalgae / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D000596:Amino Acids; D056804:Biofuels; D014280:Triglycerides; D000105:Acetyl Coenzyme A
keywords: 
  BCAA
  ; 
  TAG
  ; acetyl-CoA; biofuel; growth phase; microalga