Characterization of Early Enzymes Involved in TDP-Aminodideoxypentose Biosynthesis en Route to Indolocarbazole AT2433

Chembiochem. 2015 Oct 12;16(15):2141-6. doi: 10.1002/cbic.201500365. Epub 2015 Sep 18.

Abstract

The characterization of TDP-α-D-glucose dehydrogenase (AtmS8), TDP-α-D-glucuronic acid decarboxylase (AtmS9), and TDP-4-keto-α-D-xylose 2,3-dehydratase (AtmS14), involved in Actinomadura melliaura AT2433 aminodideoxypentose biosynthesis, is reported. This study provides the first biochemical evidence that both deoxypentose and deoxyhexose biosynthetic pathways share common strategies for sugar 2,3-dehydration/reduction and implicates the sugar nucleotide base specificity of AtmS14 as a potential mechanism for sugar nucleotide commitment to secondary metabolism. In addition, a re-evaluation of the AtmS9 homologue involved in calicheamicin aminodeoxypentose biosynthesis (CalS9) reveals that CalS9 catalyzes UDP-4-keto-α-D-xylose as the predominant product, rather than UDP-α-D-xylose as previously reported. Cumulatively, this work provides additional fundamental insights regarding the biosynthesis of novel pentoses attached to complex bacterial secondary metabolites.

Keywords: decarboxylases; dehydratases; dehydrogenases; natural products; sugar nucleotides.

Publication types

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

MeSH terms

  • Carbazoles / chemistry
  • Carbazoles / metabolism*
  • Glucose 1-Dehydrogenase / chemistry
  • Glucose 1-Dehydrogenase / metabolism*
  • Glutamate Decarboxylase / chemistry
  • Glutamate Decarboxylase / metabolism*
  • Hydro-Lyases / chemistry
  • Hydro-Lyases / metabolism*
  • Molecular Structure
  • Nucleoside Diphosphate Sugars / biosynthesis*
  • Proton Magnetic Resonance Spectroscopy

Substances

  • Carbazoles
  • Nucleoside Diphosphate Sugars
  • Glucose 1-Dehydrogenase
  • Glutamate Decarboxylase
  • Hydro-Lyases