13C Metabolic Flux Analysis of acetate conversion to lipids by Yarrowia lipolytica

Liu, Nian; Qiao, Kangjian; Stephanopoulos, Gregory

doi:10.1016/j.ymben.2016.06.006

Title: ¹³C Metabolic Flux Analysis of acetate conversion to lipids by Yarrowia lipolytica

Journal Article · Tue Jul 05 00:00:00 EDT 2016 · Metabolic Engineering

DOI:https://doi.org/10.1016/j.ymben.2016.06.006· OSTI ID:1534386

Liu, Nian ^[1]; Qiao, Kangjian ^[1]; Stephanopoulos, Gregory ^[1]

Massachusetts Institute of Technology (MIT), Cambridge, MA (United States)

We report volatile fatty acids (VFAs) are an inexpensive and renewable carbon source that can be generated from gas fermentation and anaerobic digestion of fermentable wastes. The oleaginous yeast Yarrowia lipolytica is a promising biocatalyst that can utilize VFAs and convert them into triacylglycerides (TAGs). However, currently there is limited knowledge on the metabolism of Y. lipolytica when cultured on VFAs. To develop a better understanding, we used acetate as the sole carbon source to culture two strains, a control strain and a previously engineered strain for lipid overaccumulation. For both strains, metabolism during the growth phase and lipid production phase were investigated by metabolic flux analysis using two parallel sodium acetate tracers. The resolved flux distributions demonstrate that the glyoxylate shunt pathway is constantly active and the flux through gluconeogenesis varies depending on strain and phase. In particular, by regulating the activities of malate transport and pyruvate kinase, the cells divert only a portion of the glyoxylate shunt flux required to satisfy the needs for anaplerotic reactions and NADPH production through gluconeogenesis and the oxidative pentose phosphate pathway (PPP). Excess flux flows back to the tricarboxylic acid (TCA) cycle for energy production. As with the case of glucose as the substrate, the primary source for lipogenic NADPH is derived from the oxidative PPP.

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Research Organization:: Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: SC0008744

OSTI ID:: 1534386

Alternate ID(s):: OSTI ID: 1396975

Journal Information:: Metabolic Engineering, Vol. 38, Issue C; ISSN 1096-7176

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 49 works

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59 BASIC BIOLOGICAL SCIENCES
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13C metabolic flux analysis
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gluconeogenesis

Title: 13C Metabolic Flux Analysis of acetate conversion to lipids by Yarrowia lipolytica

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Title: ¹³C Metabolic Flux Analysis of acetate conversion to lipids by Yarrowia lipolytica