Expanding Upon Styrene Biosynthesis to Engineer a Novel Route to 2-Phenylethanol

Biotechnol J. 2017 Oct;12(10). doi: 10.1002/biot.201700310. Epub 2017 Sep 4.

Abstract

2-Phenylethanol (2PE) is a key molecule used in the fragrance and food industries, as well as a potential biofuel. In contrast to its extraction from plant biomass and/or more common chemical synthesis, microbial 2PE production has been demonstrated via both native and heterologous expression of the yeast Ehrlich pathway. Here, a novel alternative to this established pathway is systematically engineered in Escherichia coli and evaluated as a more robust and efficient route. This novel pathway is constructed via the modular extension of a previously engineered styrene biosynthesis pathway, proceeding from endogenous l-phenylalanine in five steps and involving four heterologous enzymes. This "styrene-derived" pathway boasts nearly a 10-fold greater thermodynamic driving force than the Ehrlich pathway, and enables reduced accumulation of acetate byproduct. When directly compared using a host strain engineered for l-phenylalanine over-production, preservation of phosphoenolpyruvate, and reduced formation of byproduct 2-phenylacetic acid, final 2PE titers via the styrene-derived and Ehrlich pathways reached 1817 and 1164 mg L-1 , respectively, at yields of 60.6 and 38.8 mg g-1 . Following optimization of induction timing and initial glucose loading, 2PE titers by the styrene-derived pathway approached 2 g L-1 - nearly a two-fold twofold increase over prior reports for 2PE production by E. coli employing the Ehrlich pathway.

Keywords: 2-phenylethanol; L-phenylalanine; aromatics; styrene; styrene oxide.

MeSH terms

  • Acetates / metabolism
  • Biosynthetic Pathways / genetics*
  • Biosynthetic Pathways / physiology
  • Escherichia coli / drug effects
  • Escherichia coli / enzymology
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Glucose / metabolism
  • Isomerases / metabolism
  • Metabolic Engineering*
  • Phenylacetates / metabolism
  • Phenylalanine / metabolism
  • Phenylethyl Alcohol / metabolism*
  • Phenylethyl Alcohol / toxicity
  • Pseudomonas putida / enzymology
  • Pseudomonas putida / genetics
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics
  • Styrene / metabolism*
  • Time Factors

Substances

  • Acetates
  • Escherichia coli Proteins
  • Phenylacetates
  • Styrene
  • Phenylalanine
  • Isomerases
  • styrene-oxide isomerase
  • phenylacetic acid
  • Glucose
  • Phenylethyl Alcohol