Engineering Saccharomyces cerevisiae to produce odd chain-length fatty alcohols

Biotechnol Bioeng. 2016 Apr;113(4):842-51. doi: 10.1002/bit.25856. Epub 2015 Nov 2.

Abstract

Fatty aldehydes and alcohols are valuable precursors used in the industrial manufacturing of a myriad of specialty products. Herein, we demonstrate the de novo production of odd chain-length fatty aldehydes and fatty alcohols in Saccharomyces cerevisiae by expressing a novel biosynthetic pathway involving cytosolic thioesterase, rice α-dioxygenase and endogenous aldehyde reductases. We attained production titers of ∼20 mg/l fatty aldehydes and ∼20 mg/l fatty alcohols in shake flask cultures after 48 and 60 h respectively without extensive fine-tuning of metabolic fluxes. In contrast to prior studies which relied on bi-functional fatty acyl-CoA reductase to produce even chain-length fatty alcohols, our biosynthetic route exploits α-oxidation reaction to produce odd chain-length fatty aldehyde intermediates without using NAD(P)H cofactor, thereby conserving cellular resource during the overall synthesis of odd chain-length fatty alcohols. The biosynthetic pathway presented in this study has the potential to enable sustainable and efficient synthesis of fatty acid-derived chemicals from processed biomass.

Keywords: fatty alcohols; fatty aldehydes; metabolic engineering; saccharomyces cerevisiae.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / metabolism
  • Biosynthetic Pathways / genetics*
  • Fatty Acids / metabolism
  • Fatty Alcohols / metabolism*
  • Gene Expression
  • Metabolic Engineering / methods*
  • Oryza
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism*

Substances

  • Aldehydes
  • Fatty Acids
  • Fatty Alcohols
  • Recombinant Proteins
  • fatty aldehyde