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

Chemistry & Biology
Vinayak AgarwalSatish K Nair

Abstract

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.

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Citations

Feb 3, 2016·Current Opinion in Chemical Biology·Jason P ChinJohn P Quinn
Jan 20, 2017·ACS Synthetic Biology·Todd S FreestoneHuimin Zhao
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Apr 1, 2017·Frontiers in Cellular and Infection Microbiology·Johanna R ElfenbeinHelene L Andrews-Polymenis
Aug 11, 2021·Chembiochem : a European Journal of Chemical Biology·Simanga R GamaDavid L Zechel

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