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Engineering Saccharomyces cerevisiae to produce odd chain‐length fatty alcohols

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. Biotechnol. Bioeng. 2016;113: 842–851. © 2015 Wiley Periodicals, Inc.