A New Microbial Pathway for Organophosphonate Degradation Catalyzed by Two Previously Misannotated Non-Heme-Iron Oxygenases

Biochemistry. 2019 Mar 26;58(12):1627-1647. doi: 10.1021/acs.biochem.9b00044. Epub 2019 Mar 7.

Abstract

The assignment of biochemical functions to hypothetical proteins is challenged by functional diversification within many protein structural superfamilies. This diversification, which is particularly common for metalloenzymes, renders functional annotations that are founded solely on sequence and domain similarities unreliable and often erroneous. Definitive biochemical characterization to delineate functional subgroups within these superfamilies will aid in improving bioinformatic approaches for functional annotation. We describe here the structural and functional characterization of two non-heme-iron oxygenases, TmpA and TmpB, which are encoded by a genomically clustered pair of genes found in more than 350 species of bacteria. TmpA and TmpB are functional homologues of a pair of enzymes (PhnY and PhnZ) that degrade 2-aminoethylphosphonate but instead act on its naturally occurring, quaternary ammonium analogue, 2-(trimethylammonio)ethylphosphonate (TMAEP). TmpA, an iron(II)- and 2-(oxo)glutarate-dependent oxygenase misannotated as a γ-butyrobetaine (γbb) hydroxylase, shows no activity toward γbb but efficiently hydroxylates TMAEP. The product, ( R)-1-hydroxy-2-(trimethylammonio)ethylphosphonate [( R)-OH-TMAEP], then serves as the substrate for the second enzyme, TmpB. By contrast to its purported phosphohydrolytic activity, TmpB is an HD-domain oxygenase that uses a mixed-valent diiron cofactor to enact oxidative cleavage of the C-P bond of its substrate, yielding glycine betaine and phosphate. The high specificities of TmpA and TmpB for their N-trimethylated substrates suggest that they have evolved specifically to degrade TMAEP, which was not previously known to be subject to microbial catabolism. This study thus adds to the growing list of known pathways through which microbes break down organophosphonates to harvest phosphorus, carbon, and nitrogen in nutrient-limited niches.

Publication types

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

MeSH terms

  • Aminoethylphosphonic Acid / analogs & derivatives*
  • Aminoethylphosphonic Acid / chemistry
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Escherichia coli / genetics
  • Humans
  • Iron / chemistry
  • Ketoglutaric Acids / chemistry
  • Organophosphonates
  • Organophosphorus Compounds / chemistry
  • Oxidation-Reduction
  • Oxygenases / chemistry*
  • Oxygenases / genetics
  • Pseudomonas / enzymology
  • Rhodobacteraceae / enzymology
  • Substrate Specificity

Substances

  • Bacterial Proteins
  • Ketoglutaric Acids
  • Organophosphonates
  • Organophosphorus Compounds
  • (2-(dimethylamino)ethyl)phosphonic acid
  • N,N,N-trimethyl-2-aminoethylphosphonate
  • Aminoethylphosphonic Acid
  • Iron
  • Oxygenases

Supplementary concepts

  • Leisingera caerulea