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

Michael S. Machas, Rebekah Mckenna, David Nielsen

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


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.

Original languageEnglish (US)
Article number1700310
JournalBiotechnology Journal
Issue number10
StatePublished - Oct 2017


  • 2-phenylethanol
  • L-phenylalanine
  • aromatics
  • styrene
  • styrene oxide

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology
  • Molecular Medicine


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