title: Establishing very long-chain fatty alcohol and wax ester biosynthesis in Saccharomyces cerevisiae.
abstract: Wax esters (WEs) are neutral lipids and can be used for a broad range of commercial applications, including personal care products, lubricants, or coatings. They are synthesized by enzymatic reactions catalyzed by a fatty acyl reductase (FAR) and a wax ester synthase (WS). At present, commercially used WEs are mainly isolated from Simmondsia chinensis (jojoba), but the high extraction costs and limited harvest areas constrain their use. The use of FARs in combination with different WSs to achieve a synthesis of jojoba-like WEs in bacteria and yeast has been reported previously, but the products were restricted to C28-C36 WEs. These rather short WEs make up only a very small percentage of the total WEs in natural jojoba oil. The synthesis of longer chain WEs (up to C44) in Saccharomyces cerevisiae has so far only been achieved after substrate feeding. Here we identified new routes for producing very long-chain fatty alcohols (VLCFOHs) up to a chain length of C22 by heterologous expression of a FAR derived from Apis mellifera (AmFAR1) or Marinobacter aquaeolei VT8 (Maqu_2220) in S. cerevisiae and achieved maximum yields of 3.22 ± 0.36 mg/g cell dry weight (CDW) and 7.84 ± 3.09 mg/g CDW, respectively, after 48 h. Moreover, we enabled the synthesis of jojoba-like WEs up to a chain length of C42, catalyzed by a combination of Maqu_2220 together with the WS from S. chinensis (SciWS) and the S. cerevisiae elongase Elo2p, with a maximum yield of 12.24 ± 3.35 mg/g CDW after 48 h. Biotechnol. Bioeng. 2017;114: 1025-1035. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Biology and Biological Engineering, Systems and Synthetic Biology, Chalmers University of Technology, Kemivägen 10, Göteborg, SE-412 96, Sweden.|Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology, Kemivägen, Göteborg, Sweden.
authors.forename: Leonie
authors.initials: L
authors.lastname: Wenning
authors.affiliation: Department of Biology and Biological Engineering, Systems and Synthetic Biology, Chalmers University of Technology, Kemivägen 10, Göteborg, SE-412 96, Sweden.|Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology, Kemivägen, Göteborg, Sweden.
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of Biology and Biological Engineering, Systems and Synthetic Biology, Chalmers University of Technology, Kemivägen 10, Göteborg, SE-412 96, Sweden.|Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology, Kemivägen, Göteborg, Sweden.
authors.forename: Florian
authors.initials: F
authors.lastname: David
authors.affiliation: Department of Biology and Biological Engineering, Systems and Synthetic Biology, Chalmers University of Technology, Kemivägen 10, Göteborg, SE-412 96, Sweden.|Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology, Kemivägen, Göteborg, Sweden.|Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kemitorvet, Lyngby, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Nielsen
authors.affiliation: Department of Biology and Biological Engineering, Systems and Synthetic Biology, Chalmers University of Technology, Kemivägen 10, Göteborg, SE-412 96, Sweden.|Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology, Kemivägen, Göteborg, Sweden.
authors.forename: Verena
authors.initials: V
authors.lastname: Siewers
mesh_terms: D000217:Acyltransferases; D000445:Aldehyde Oxidoreductases; D000818:Animals; D001516:Bees / Q000201:enzymology / Q000235:genetics; D004952:Esters / Q000737:chemistry / Q000378:metabolism*; D005233:Fatty Alcohols / Q000737:chemistry / Q000378:metabolism*; D053520:Marinobacter / Q000201:enzymology / Q000235:genetics; D060847:Metabolic Engineering / Q000379:methods*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D014885:Waxes / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004952:Esters; D005233:Fatty Alcohols; D011994:Recombinant Proteins; D014885:Waxes; C034743:jojoba wax; D000445:Aldehyde Oxidoreductases; D000217:Acyltransferases; C079165:long-chain-alcohol O-fatty-acyltransferase
keywords: Saccharomyces cerevisiae; jojoba-like wax esters; very long-chain monounsaturated fatty acids; very long-chain monounsaturated fatty alcohols