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Fermentation 2017, 3(3), 40; doi: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)
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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-Text
Keywords: Yarrowia lipolytica; long chain dicarboxylic acid; building blocks; citric acid; glycerol; genetic and metabolic engineering; fermentation; bioconversion Yarrowia lipolytica; long chain dicarboxylic acid; building blocks; citric acid; glycerol; genetic and metabolic engineering; fermentation; bioconversion
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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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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