title: Harnessing Yeast Peroxisomes for Biosynthesis of Fatty-Acid-Derived Biofuels and Chemicals with Relieved Side-Pathway Competition.
abstract: Establishing efficient synthetic pathways for microbial production of biochemicals is often hampered by competing pathways and/or insufficient precursor supply. Compartmentalization in cellular organelles can isolate synthetic pathways from competing pathways, and provide a compact and suitable environment for biosynthesis. Peroxisomes are cellular organelles where fatty acids are degraded, a process that is inhibited under typical fermentation conditions making them an interesting workhouse for production of fatty-acid-derived molecules. Here, we show that targeting synthetic pathways to peroxisomes can increase the production of fatty-acid-derived fatty alcohols, alkanes and olefins up to 700%. In addition, we demonstrate that biosynthesis of these chemicals in the peroxisomes results in significantly decreased accumulation of byproducts formed by competing enzymes. We further demonstrate that production can be enhanced up to 3-fold by increasing the peroxisome population. The strategies described here could be used for production of other chemicals, especially acyl-CoA-derived molecules.
authors.forename: Yongjin J
authors.initials: YJ
authors.lastname: Zhou
authors.forename: Nicolaas A
authors.initials: NA
authors.lastname: Buijs
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Zhu
authors.forename: Diego Orol
authors.initials: DO
authors.lastname: Gómez
authors.forename: Akarin
authors.initials: A
authors.lastname: Boonsombuti
authors.forename: Verena
authors.initials: V
authors.lastname: Siewers
authors.affiliation: Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark , DK-2800 Kgs, Lyngby, Denmark.|Science for Life Laboratory, Royal Institute of Technology , SE-17121 Stockholm, Sweden.
authors.forename: Jens
authors.initials: J
authors.lastname: Nielsen
mesh_terms: D056804:Biofuels; D005227:Fatty Acids / Q000737:chemistry* / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D015394:Molecular Structure; D020675:Peroxisomes / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000378:metabolism*
chemical_list: D056804:Biofuels; D005227:Fatty Acids