Fermentation 2017, 3(3), 40; https://doi.org/10.3390/fermentation3030040
Combinatorial Engineering of Yarrowia lipolytica as a Promising Cell Biorefinery Platform for the de novo Production of Multi-Purpose Long Chain Dicarboxylic Acids
1
Department of Biological Systems Engineering, Bioprocessing and Bioproducts Engineering Laboratory, Washington State University, Pullman, WA 99163, USA
2
UMR 782 GMPA, CBAI, INRA—AgroParisTech-Université Paris-Saclay, F-78850 Thiverval Grignon, France
*
Authors to whom correspondence should be addressed.
Received: 22 July 2017 / Revised: 7 August 2017 / Accepted: 8 August 2017 / Published: 18 August 2017
(This article belongs to the Special Issue Yeast Biotechnology 2.0)
Abstract
This proof-of-concept study establishes Yarrowia lipolytica (Y. lipolytica) as a whole cell factory for the de novo production of long chain dicarboxylic acid (LCDCA-16 and 18) using glycerol as the sole source of carbon. Modification of the fatty acid metabolism pathway enabled creating a pool of fatty acids in a β-oxidation deficient strain. We then selectively upregulated the native fatty acid ω-oxidation pathway for the enhanced terminal oxidation of the endogenous fatty acid precursors. Nitrogen-limiting conditions and leucine supplementation were employed to induce fatty acid biosynthesis in an engineered Leu− modified strain. Our genetic engineering strategy allowed a minimum production of 330 mg/L LCDCAs in shake flask. Scale up to a 1-L bioreactor increased the titer to 3.49 g/L. Our engineered yeast also produced citric acid as a major by-product at a titer of 39.2 g/L. These results provide basis for developing Y. lipolytica as a safe biorefinery platform for the sustainable production of high-value LCDCAs from non-oily feedstock. View Full-TextKeywords:
Yarrowia lipolytica; long chain dicarboxylic acid; building blocks; citric acid; glycerol; genetic and metabolic engineering; fermentation; bioconversion
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Abghari, A.; Madzak, C.; Chen, S. Combinatorial Engineering of Yarrowia lipolytica as a Promising Cell Biorefinery Platform for the de novo Production of Multi-Purpose Long Chain Dicarboxylic Acids. Fermentation 2017, 3, 40.
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