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Updated: Apr 18, 2026

Biosynthesis of a Flavonol from a Flavanone by Establishing a One-pot Bienzymatic Cascade
Published on: August 14, 2019
Biosynthesis of fosfazinomycin is a convergent process
Zedu Huang1, Kwo-Kwang A Wang1, Jaeheon Lee2
1Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801. ; Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801. ; Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
Abstract:
Fosfazinomycin A is a phosphonate natural product in which the C-terminal carboxylate of a Val-Arg dipeptide is connected to methyl 2-hydroxy-2-phosphono-acetate (Me-HPnA) via a unique hydrazide linkage. We report here that Me-HPnA is generated from phosphonoacetaldehyde (PnAA) in three biosynthetic steps through the combined action of an O-methyltransferase (FzmB) and an α-ketoglutarate (α-KG) dependent non-heme iron dioxygenase (FzmG). Unexpectedly, the latter enzyme is involved in two different steps, oxidation of the PnAA to phosphonoacetic acid as well as hydroxylation of methyl 2-phosphonoacetate. The N-methyltransferase (FzmH) was able to methylate Arg-NHNH2 (3) to give Arg-NHNHMe (4), constituting the second segment of the fosfazinomycin molecule. Methylation of other putative intermediates such as desmethyl fosfazinomycin B was not observed. Collectively, our current data support a convergent biosynthetic pathway to fosfazinomycin.
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