Functional assignment of multiple catabolic pathways for D-apiose

Nat Chem Biol. 2018 Jul;14(7):696-705. doi: 10.1038/s41589-018-0067-7. Epub 2018 Jun 4.


Colocation of the genes encoding ABC, TRAP, and TCT transport systems and catabolic pathways for the transported ligand provides a strategy for discovering novel microbial enzymes and pathways. We screened solute-binding proteins (SBPs) for ABC transport systems and identified three that bind D-apiose, a branched pentose in the cell walls of higher plants. Guided by sequence similarity networks (SSNs) and genome neighborhood networks (GNNs), the identities of the SBPs enabled the discovery of four catabolic pathways for D-apiose with eleven previously unknown reactions. The new enzymes include D-apionate oxidoisomerase, which catalyzes hydroxymethyl group migration, as well as 3-oxo-isoapionate-4-phosphate decarboxylase and 3-oxo-isoapionate-4-phosphate transcarboxylase/hydrolase, which are RuBisCO-like proteins (RLPs). The web tools for generating SSNs and GNNs are publicly accessible ( ), so similar 'genomic enzymology' strategies for discovering novel pathways can be used by the community.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biocatalysis
  • Humans
  • Isomerases / genetics
  • Isomerases / metabolism
  • Models, Molecular
  • Pentoses / chemistry
  • Pentoses / metabolism*


  • Pentoses
  • apiose
  • Isomerases