Structure and function of phosphonoacetaldehyde dehydrogenase: The missing link in phosphonoacetate formation

Vinayak Agarwal, Spencer C. Peck, Jui Hui Chen, Svetlana A. Borisova, Jonathan R. Chekan, Wilfred A. Van Der Donk, Satish K. Nair

Research output: Contribution to journalArticlepeer-review

Abstract

Summary Phosphonates (C-PO32-) have applications as antibiotics, herbicides, and detergents. In some environments, these molecules represent the predominant source of phosphorus, and several microbes have evolved dedicated enzymatic machineries for phosphonate degradation. For example, most common naturally occurring phosphonates can be catabolized to either phosphonoacetaldehyde or phosphonoacetate, which can then be hydrolyzed to generate inorganic phosphate and acetaldehyde or acetate, respectively. The phosphonoacetaldehyde oxidase gene (phnY) links these two hydrolytic processes and provides a previously unknown catabolic mechanism for phosphonoacetate production in the microbial metabolome. Here, we present biochemical characterization of PhnY and high-resolution crystal structures of the apo state, as well as complexes with substrate, cofactor, and product. Kinetic analysis of active site mutants demonstrates how a highly conserved aldehyde dehydrogenase active site has been modified in nature to generate activity with a phosphonate substrate.

Original languageEnglish (US)
Pages (from-to)125-135
Number of pages11
JournalChemistry and Biology
Volume21
Issue number1
DOIs
StatePublished - Jan 16 2014

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Fingerprint

Dive into the research topics of 'Structure and function of phosphonoacetaldehyde dehydrogenase: The missing link in phosphonoacetate formation'. Together they form a unique fingerprint.

Cite this