Engineering nonphosphorylative metabolism to generate lignocellulose-derived products

Nat Chem Biol. 2016 Apr;12(4):247-53. doi: 10.1038/nchembio.2020. Epub 2016 Feb 8.

Abstract

Conversion of lignocellulosic biomass into value-added products provides important environmental and economic benefits. Here we report the engineering of an unconventional metabolism for the production of tricarboxylic acid (TCA)-cycle derivatives from D-xylose, L-arabinose and D-galacturonate. We designed a growth-based selection platform to identify several gene clusters functional in Escherichia coli that can perform this nonphosphorylative assimilation of sugars into the TCA cycle in less than six steps. To demonstrate the application of this new metabolic platform, we built artificial biosynthetic pathways to 1,4-butanediol (BDO) with a theoretical molar yield of 100%. By screening and engineering downstream pathway enzymes, 2-ketoacid decarboxylases and alcohol dehydrogenases, we constructed E. coli strains capable of producing BDO from D-xylose, L-arabinose and D-galacturonate. The titers, rates and yields were higher than those previously reported using conventional pathways. This work demonstrates the potential of nonphosphorylative metabolism for biomanufacturing with improved biosynthetic efficiencies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Arabinose / metabolism*
  • Biosynthetic Pathways
  • Butylene Glycols / metabolism*
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Hexuronic Acids / metabolism*
  • Ketoglutaric Acids / metabolism
  • Lignin / metabolism*
  • Metabolic Engineering
  • Multigene Family
  • Xylose / metabolism*

Substances

  • Butylene Glycols
  • Hexuronic Acids
  • Ketoglutaric Acids
  • lignocellulose
  • galacturonic acid
  • 1,4-butanediol
  • Lignin
  • Xylose
  • Arabinose