3′‐Enolpyruvyl‐UMP, a Novel and Unexpected Metabolite in Nikkomycin Biosynthesis

Abstract

An unexpected turn. NikO, the putative enolpyruvyl transferase involved in the formation of the aminohexuronic acid moiety of nikkomycins catalyzes the formation of 3′‐enolpyruvyl‐UMP from UMP (see scheme). This finding contradicts the current model for the biosynthesis of aminohexuronic acid.

Structural and Functional Characterization of NikO, an Enolpyruvyl Transferase Essential in Nikkomycin Biosynthesis

“…Initially, it was proposed that NikO uses uridine as a substrate (3,7). However, attempts to demonstrate the transfer of an enolpyruvyl moiety to uridine failed and led to the discovery that UMP is the cognate substrate of the enzyme (8).…”

“…NikO was annotated as an enolpyruvyl transferase showing highest sequence identity to bacterial UDP-N-acetylglucosamine enolpyruvyl transferases (MurA) from various species (ϳ30%). We could demonstrate that NikO is, indeed, an enolpyruvyl transferase catalyzing the transfer of the enolpyruvyl moiety from PEP to the 3Ј-hydroxyl group of UMP (Scheme 1) (8). It is also assumed that NikO catalyzes the corresponding reaction with 5Ј-phosphoribofuranosyl-4-formyl-4-imidazolin-2-one because disruption of the nikO gene leads to the accumulation of ribofuranosyl-4-formyl-4-imidazolone (7).…”

Enhancement of the Diversity of Polyoxins by a Thymine-7-Hydroxylase Homolog outside the Polyoxin Biosynthesis Gene Cluster

“…It was deduced that the nucleoside moiety originated from the condensation of uridine with phosphoenolpyruvate (PEP) to generate octosyl acid as the intermediate (7,12,14). Then, a subsequent oxidative elimination of the two terminal carbons would create the nucleoside moiety (12).…”

Construction of an octosyl acid backbone catalyzed by a radical S-adenosylmethionine enzyme and a phosphatase in the biosynthesis of high-carbon sugar nucleoside antibiotics

“…In addition, the orthologous enzymes encoded by nikO 11 and polA 4 have been shown to catalyze the formation of 3′-enoylpyruvaoyl-UMP (3′-EUMP) from PEP and UMP. Taken together, these observations allowed us to propose a preliminary biosynthetic pathway for OA, which consisted of two key steps: (i) the oxidative dephosphorylation of 3′-EUMP catalyzed by PolJ, and (ii) the cyclization of octofuranulose-uronic acid (OFUA) to OA through a radical reaction catalyzed by PolH (Scheme 1A).…”