Lipid production in Yarrowia lipolytica is maximized by engineering cytosolic redox metabolism

Kangjian Qiao, Thomas M. Wasylenko, Kang Zhou, Peng Xu, Gregory Stephanopoulos*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

334 Scopus citations


Microbial factories have been engineered to produce lipids from carbohydrate feedstocks for production of biofuels and oleochemicals. However, even the best yields obtained to date are insufficient for commercial lipid production. To maximize the capture of electrons generated from substrate catabolism and thus increase substrate-to-product yields, we engineered 13 strains of Yarrowia lipolytica with synthetic pathways converting glycolytic NADH into the lipid biosynthetic precursors NADPH or acetyl-CoA. A quantitative model was established and identified the yield of the lipid pathway as a crucial determinant of overall process yield. The best engineered strain achieved a productivity of 1.2 g/L/h and a process yield of 0.27 g-fatty acid methyl esters/g-glucose, which constitutes a 25% improvement over previously engineered yeast strains. Oxygen requirements of our highest producer were reduced owing to decreased NADH oxidization by aerobic respiration. We show that redox engineering could enable commercialization of microbial carbohydrate-based lipid production.

Original languageEnglish
Pages (from-to)173-177
Number of pages5
JournalNature Biotechnology
Issue number2
StatePublished - 1 Feb 2017
Externally publishedYes


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