Engineering Yarrowia lipolytica as a platform for synthesis of drop-in transportation fuels and oleochemicals

Xu, Peng; Qiao, Kangjian; Ahn, Woo Suk; Stephanopoulos, Gregory

doi:10.1073/pnas.1607295113

Title: Engineering Yarrowia lipolytica as a platform for synthesis of drop-in transportation fuels and oleochemicals

Journal Article · Mon Sep 12 00:00:00 EDT 2016 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.1607295113· OSTI ID:1470051

Xu, Peng ^[1]; Qiao, Kangjian ^[1]; Ahn, Woo Suk ^[1]; Stephanopoulos, Gregory ^[1]

Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Dept. of Chemical Engineering

Harnessing lipogenic pathways and rewiring acyl-CoA and acyl-ACP (acyl carrier protein) metabolism in Yarrowia lipolytica hold great potential for cost-efficient production of diesel, gasoline-like fuels, and oleochemicals. Here we assessed various pathway engineering strategies in Y. lipolytica toward developing a yeast biorefinery platform for sustainable production of fuel-like molecules and oleochemicals. Specifically, acyl-CoA/acyl-ACP processing enzymes were targeted to the cytoplasm, peroxisome, or endoplasmic reticulum to generate fatty acid ethyl esters and fatty alkanes with tailored chain length. Activation of endogenous free fatty acids and the subsequent reduction of fatty acyl-CoAs enabled the efficient synthesis of fatty alcohols. Engineering a hybrid fatty acid synthase shifted the free fatty acids to a medium chain-length scale. Manipulation of alternative cytosolic acetyl-CoA pathways partially decoupled lipogenesis from nitrogen starvation and unleashed the lipogenic potential of Y. lipolytica. Finally, taken together, the strategies reported here represent promising steps to develop a yeast biorefinery platform that potentially upgrades low-value carbons to high-value fuels and oleochemicals in a sustainable and environmentally friendly manner.

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

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: SC0008744

OSTI ID:: 1470051

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, Issue 39; ISSN 0027-8424

Publisher:: National Academy of Sciences, Washington, DC (United States)Copyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 285 works

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Microbial bioconversion of thermally depolymerized polypropylene by Yarrowia lipolytica for fatty acid production Mihreteab, Merhawi; Stubblefield, Bryan A.; Gilbert, Eric S. Applied Microbiology and Biotechnology, Vol. 103, Issue 18 https://doi.org/10.1007/s00253-019-09999-2	journal	July 2019
Scalable web services for the PSIPRED Protein Analysis Workbench Buchan, Daniel W. A.; Minneci, Federico; Nugent, Tim C. O. Nucleic Acids Research, Vol. 41, Issue W1 https://doi.org/10.1093/nar/gkt381	journal	June 2013
Engineering Saccharomyces cerevisiae cells for production of fatty acid-derived biofuels and chemicals Hu, Yating; Zhu, Zhiwei; Nielsen, Jens Open Biology, Vol. 9, Issue 5 https://doi.org/10.1098/rsob.190049	journal	May 2019
Boosting the biosynthesis of betulinic acid and related triterpenoids in Yarrowia lipolytica via multimodular metabolic engineering Jin, Cong-Cong; Zhang, Jin-Lai; Song, Hao Microbial Cell Factories, Vol. 18, Issue 1 https://doi.org/10.1186/s12934-019-1127-8	journal	May 2019
Drop-in biofuel production using fatty acid photodecarboxylase from Chlorella variabilis in the oleaginous yeast Yarrowia lipolytica Bruder, Stefan; Moldenhauer, Eva Johanna; Lemke, Robert Denis Biotechnology for Biofuels, Vol. 12, Issue 1 https://doi.org/10.1186/s13068-019-1542-4	journal	August 2019
Substrates and oxygen dependent citric acid production by Yarrowia lipolytica: insights through transcriptome and fluxome analyses Sabra, Wael; Bommareddy, Rajesh Reddy; Maheshwari, Garima BioMed Central https://doi.org/10.15480/882.1496	text	January 2017
Engineering of Fatty Acid Synthases (FASs) to Boost the Production of Medium-Chain Fatty Acids (MCFAs) in Mucor circinelloides Hussain, Syed; Hameed, Ahsan; Khan, Md. International Journal of Molecular Sciences, Vol. 20, Issue 3 https://doi.org/10.3390/ijms20030786	journal	February 2019
Multi-Omics Analysis of Fatty Alcohol Production in Engineered Yeasts Saccharomyces cerevisiae and Yarrowia lipolytica Dahlin, Jonathan; Holkenbrink, Carina; Marella, Eko Roy RWTH Aachen University https://doi.org/10.18154/rwth-2019-09056	text	January 2019
Understanding lipogenesis by dynamically profiling transcriptional activity of lipogenic promoters in Yarrowia lipolytica Liu, Huan; Marsafari, Monireh; Deng, Li Springer Nature Switzerland AG. https://doi.org/10.13016/m2uh8f-x3as	collection	January 2019
Corrigendum: Multi-Omics Analysis of Fatty Alcohol Production in Engineered Yeasts Saccharomyces cerevisiae and Yarrowia lipolytica Dahlin, Jonathan; Holkenbrink, Carina; Marella, Eko Roy Frontiers in Genetics, Vol. 11 https://doi.org/10.3389/fgene.2020.637738	journal	January 2021
CRISPR-Cas12a/Cpf1-assisted precise, efficient and multiplexed genome-editing in Yarrowia lipolytica Yang, Zhiliang; Edwards, Harley; Xu, Peng Metabolic Engineering Communications, Vol. 10 https://doi.org/10.1016/j.mec.2019.e00112	journal	June 2020
Application of Stable Isotope Tracing to Elucidate Metabolic Dynamics During Yarrowia lipolytica α-Ionone Fermentation Czajka, Jeffrey J.; Kambhampati, Shrikaar; Tang, Yinjie J. iScience, Vol. 23, Issue 2 https://doi.org/10.1016/j.isci.2020.100854	journal	February 2020
YaliBricks, a versatile genetic toolkit for streamlined and rapid pathway engineering in Yarrowia lipolytica Wong, Lynn; Engel, Jake; Jin, Erqing Metabolic Engineering Communications, Vol. 5 https://doi.org/10.1016/j.meteno.2017.09.001	journal	December 2017
Systems and Synthetic Biology Approaches to Engineer Fungi for Fine Chemical Production Martins-Santana, Leonardo; Nora, Luisa C.; Sanches-Medeiros, Ananda Frontiers in Bioengineering and Biotechnology, Vol. 6 https://doi.org/10.3389/fbioe.2018.00117	journal	October 2018

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