Engineering β-oxidation in Yarrowia lipolytica for methyl ketone production

Metabolic Engineering
Erik K R HankoJay D Keasling

Abstract

Medium- and long-chain methyl ketones are fatty acid-derived compounds that can be used as biofuel blending agents, flavors and fragrances. However, their large-scale production from sustainable feedstocks is currently limited due to the lack of robust microbial biocatalysts. The oleaginous yeast Yarrowia lipolytica is a promising biorefinery platform strain for the production of methyl ketones from renewable lignocellulosic biomass due to its natively high flux towards fatty acid biosynthesis. In this study, we report the metabolic engineering of Y. lipolytica to produce long- and very long-chain methyl ketones. Truncation of peroxisomal β-oxidation by chromosomal deletion of pot1 resulted in the biosynthesis of saturated, mono-, and diunsaturated methyl ketones in the C13-C23 range. Additional overexpression and peroxisomal targeting of a heterologous bacterial methyl ketone biosynthesis pathway yielded an initial titer of 151.5 mg/L of saturated methyl ketones. Dissolved oxygen concentrations in the cultures were found to substantially impact cell morphology and methyl ketone biosynthesis. Bioreactor cultivation under optimized conditions resulted in a titer of 314.8 mg/L of total methyl ketones, representing more than a 600...Continue Reading

References

Jul 21, 1989·Science·R T MasonD Crews
Mar 1, 1985·The Journal of Cell Biology·P GreenspanS D Fowler
Apr 1, 1997·FEMS Microbiology Reviews·G Barth, C Gaillardin
Aug 1, 1997·Applied Microbiology and Biotechnology·D C ChenC Gaillardin
Apr 27, 2000·Journal of Bacteriology·G PignèdeJ M Nicaud
Apr 29, 2000·The Journal of Biological Chemistry·J J SmithR A Rachubinski
Jan 30, 2002·The Journal of Cell Biology·Vladimir I TitorenkoRichard A Rachubinski
Sep 19, 2002·Advances in Applied Microbiology·Colin Ratledge, James P Wynn
Nov 11, 2003·Journal of Microbiological Methods·P FickersJ M Nicaud
Jul 14, 2006·Proceedings of the National Academy of Sciences of the United States of America·Jason HillDouglas Tiffany
Aug 8, 2006·Archives of Biochemistry and Biophysics·Raúl G FerreyraMario R Ermácora
Aug 28, 2007·Bioresource Technology·C AngerbauerG M Guebitz
May 1, 2008·The Journal of Biological Chemistry·Paul A GrimsrudDavid A Bernlohr
Aug 12, 2008·Applied Microbiology and Biotechnology·Qiang LiDehua Liu
Apr 14, 2009·Nature Methods·Daniel G GibsonHamilton O Smith
Sep 2, 2009·Progress in Lipid Research·Athanasios BeopoulosJean-Marc Nicaud
Jan 20, 2010·Biotechnology Journal·Pamela P Peralta-Yahya, Jay D Keasling
Jun 29, 2011·Free Radical Biology & Medicine·Piotr Zimniak
Nov 1, 2011·Applied and Environmental Microbiology·Ee-Been GohHarry R Beller
Mar 1, 2012·Bioresource Technology·Silvia GalafassiConcetta Compagno
Aug 2, 2012·Journal of Industrial Microbiology & Biotechnology·John ParkRamon Gonzalez
Apr 23, 2013·Journal of Biotechnology·John BlazeckHal S Alper
Jan 20, 2012·ACS Synthetic Biology·Nathan J HillsonJay D Keasling
May 21, 2013·Applied and Environmental Microbiology·Jana MüllerHarry R Beller
Dec 4, 2014·Metabolic Engineering·Xueyang FengHuimin Zhao
Feb 11, 2015·Metabolic Engineering·Brian F PflegerJens Nielsen
Mar 4, 2015·Metabolic Engineering·Kangjian QiaoGregory Stephanopoulos
Apr 15, 2015·ACS Synthetic Biology·Michael E LeeJohn E Dueber
Apr 19, 2015·Biochimica Et Biophysica Acta·Rémi DulermoJean-Marc Nicaud
May 8, 2015·Applied Microbiology and Biotechnology·Catherine Madzak
Oct 20, 2015·Current Opinion in Chemical Biology·Leo d'EspauxJay D Keasling
Oct 30, 2016·Metabolic Engineering·Rodrigo Ledesma-AmaroJean-Marc Nicaud
Jul 3, 2016·FEMS Yeast Research·Hiroshi NishikawaHiroshi Mukae
Sep 14, 2016·Proceedings of the National Academy of Sciences of the United States of America·Peng XuGregory Stephanopoulos

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Citations

Apr 16, 2019·Biotechnology and Bioengineering·Jie DongSteven W Singer
Mar 18, 2020·Critical Reviews in Food Science and Nutrition·Muhammad BilalHairong Cheng
Mar 30, 2019·Microbial Cell Factories·Rui SilvaLucília Domingues
Mar 27, 2020·The Journal of Cell Biology·Fred D MastJohn D Aitchison
Feb 27, 2021·Frontiers in Bioengineering and Biotechnology·Hannah C YocumNancy A Da Silva
Feb 26, 2021·Biotechnology Advances·Atrayee ChattopadhyayMrinal K Maiti
Apr 26, 2019·Metabolic Engineering·Qiang Yan, Brian F Pfleger
Mar 16, 2019·Current Opinion in Biotechnology·Michael SpagnuoloMark Blenner
Jul 30, 2018·Metabolic Engineering·Ahmad M Abdel-MawgoudHal S Alper
Aug 19, 2020·Metabolic Engineering·Salome C NiesBirgitta E Ebert
Jun 27, 2021·Nature Reviews. Microbiology·Jay KeaslingEric Sundstrom
Sep 6, 2020·New Biotechnology·Víctor de LorenzoMarkus Schmidt

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