Article
Biosynthesis of 2-Hydroxyethylphosphonate, an Unexpected Intermediate Common to Multiple Phosphonate Biosynthetic Pathways
Journal of Biological Chemistry
(2008)
Abstract
Phosphonic acids encompass a common yet chemically diverse class of natural products that often possess potent biological activities. Here we report that, despite the significant structural differences among many of these compounds, their biosynthetic routes contain an unexpected common intermediate, 2-hydroxyethyl-phosphonate, which is synthesized from phosphonoacetaldehyde by a distinct family of metal-dependent alcohol dehydrogenases (ADHs). Although the sequence identity of the ADH family members is relatively low (34–37%), in vitro biochemical characterization of the homologs involved in biosynthesis of the antibiotics fosfomycin, phosphinothricin tripeptide, and dehydrophos (formerly A53868) unequivocally confirms their enzymatic activities. These unique ADHs have exquisite substrate specificity, unusual metal requirements, and an unprecedented monomeric quaternary structure. Further, sequence analysis shows that these ADHs form a monophyletic group along with additional family members encoded by putative phosphonate biosynthetic gene clusters. Thus, the reduction of phosphonoacetaldehyde to hydroxyethyl-phosphonate may represent a common step in the biosynthesis of many phosphonate natural products, a finding that lends insight into the evolution of phosphonate biosynthetic pathways and the chemical structures of new C–P containing secondary metabolites.
Disciplines
Publication Date
August 22, 2008
DOI
10.1074/jbc.M801788200
Publisher Statement
This article is published as Shao, Zengyi, Joshua AV Blodgett, Benjamin T. Circello, Andrew C. Eliot, Ryan Woodyer, Gongyong Li, Wilfred A. Van Der Donk, William W. Metcalf, and Huimin Zhao. "Biosynthesis of 2-hydroxyethylphosphonate, an unexpected intermediate common to multiple phosphonate biosynthetic pathways." Journal of Biological Chemistry 283, no. 34 (2008): 23161-23168. 10.1074/jbc.M801788200. Posted with permission.
Citation Information
Zengyi Shao, Joshua A.V. Blodgett, Benjamin T Circello, Andrew C Eliot, et al.. "Biosynthesis of 2-Hydroxyethylphosphonate, an Unexpected Intermediate Common to Multiple Phosphonate Biosynthetic Pathways" Journal of Biological Chemistry Vol. 283 Iss. 34 (2008) p. 23161 - 23168 Available at: http://works.bepress.com/zengyi_shao/11/