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

Oberdorfer, Gustav; Binter, Alexandra; Ginj, Cristian; Macheroux, Peter; Gruber, Karl

doi:10.1074/jbc.m112.352096

Cited by 16 publications

(9 citation statements)

References 49 publications

(33 reference statements)

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“…145,146 The orthologous enzymes encoded by nikO 147,148 and polA 145 have been shown to catalyze the formation of 3′-enoylpyruvoyl-UMP from PEP ( 108 ) and UMP in assays with purified recombinant proteins. Gene knockout experiments demonstrated that nikO 149 and sanX 146 are required for the biosynthesis of nikkomycins and that polA is required for the biosynthesis of polyoxins.…”

Section: Compounds Containing High-carbon Sugarsmentioning

confidence: 99%

The biosynthesis of nitrogen-, sulfur-, and high-carbon chain-containing sugars

2013

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Carbohydrates serve many structural and functional roles in biology. While the majority of monosaccharides are characterized by the chemical composition: (CH2O)n, modifications including deoxygenation, C-alkylation, amination, O- and N-methylation, which are characteristic of many sugar appendages of secondary metabolites, are not uncommon. Interestingly, some sugar molecules are formed via modifications including amine oxidation, sulfur incorporation, and “high-carbon” chain attachment. Most of these unusual sugars have been identified over the past several decades as components of microbially produced natural products, although a few high-carbon sugars are also found in the lipooligosaccharides of the outer cell walls of Gram-negative bacteria. Despite their broad distribution in nature, these sugars are considered “rare” due to their relative scarcity. The biosynthetic steps that underlie their formation continue to perplex researchers to this day and many questions regarding key transformations remain unanswered. This review will focus on our current understanding of the biosynthesis of unusual sugars bearing oxidized amine substituents, thio-functional groups, and high-carbon chains.

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Section: Compounds Containing High-carbon Sugarsmentioning

confidence: 99%

The biosynthesis of nitrogen-, sulfur-, and high-carbon chain-containing sugars

2013

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“…These values are comparable to those reported for the conversion of UMP to EP-UMP by NikO ( k cat / K m = 0.10 – 0.45 min −1 µM −1 ). 13 The low K m values support high specificity of NikJ and PolH towards EP-UMP. Together with the previously established relevance of octosyl acid to PN biosynthesis, 5 – 7 these observations suggest that the observed OAP synthase activity is likely the physiologically relevant function of NikJ and PolH.…”

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confidence: 91%

Carbon extension in peptidylnucleoside biosynthesis by radical SAM enzymes

Lilla

Yokoyama

2016

Nat Chem Biol

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Nikkomycins and polyoxins are antifungal peptidylnucleoside (PN) antibiotics active against human and plant pathogens. Here, we report that during PN biosynthesis in Streptomyces cacaoi and Streptomyces tendae, the C5′-extension of the nucleoside essential for downstream structural diversification is catalyzed by a conserved radical S-adenosyl-L-methionine (SAM) enzyme, PolH or NikJ. This is distinct from the nucleophilic mechanism reported for antibacterial nucleosides and represents a novel mechanism of nucleoside natural product biosynthesis.

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“…NikO was shown to transfer the enol-pyruvyl moiety from PEP to the 3′-hydroxyl group of UMP and to be inactivated by fosfomycin because of alkylation of Cys130. However, the degree of inactivation is not as pronounced as in the case of common MurA enzymes [23].…”

Section: Enol-pyruvylation In Peptidoglycan Biosynthesismentioning

confidence: 99%

Pyruvate Substitutions on Glycoconjugates

Hager

Sützl

Stefanović

et al. 2019

IJMS

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Glycoconjugates are the most diverse biomolecules of life. Mostly located at the cell surface, they translate into cell-specific “barcodes” and offer a vast repertoire of functions, including support of cellular physiology, lifestyle, and pathogenicity. Functions can be fine-tuned by non-carbohydrate modifications on the constituting monosaccharides. Among these modifications is pyruvylation, which is present either in enol or ketal form. The most commonly best-understood example of pyruvylation is enol-pyruvylation of N-acetylglucosamine, which occurs at an early stage in the biosynthesis of the bacterial cell wall component peptidoglycan. Ketal-pyruvylation, in contrast, is present in diverse classes of glycoconjugates, from bacteria to algae to yeast—but not in humans. Mild purification strategies preventing the loss of the acid-labile ketal-pyruvyl group have led to a collection of elucidated pyruvylated glycan structures. However, knowledge of involved pyruvyltransferases creating a ring structure on various monosaccharides is scarce, mainly due to the lack of knowledge of fingerprint motifs of these enzymes and the unavailability of genome sequences of the organisms undergoing pyruvylation. This review compiles the current information on the widespread but under-investigated ketal-pyruvylation of monosaccharides, starting with different classes of pyruvylated glycoconjugates and associated functions, leading to pyruvyltransferases, their specificity and sequence space, and insight into pyruvate analytics.

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

Cited by 16 publications

References 49 publications

The biosynthesis of nitrogen-, sulfur-, and high-carbon chain-containing sugars

The biosynthesis of nitrogen-, sulfur-, and high-carbon chain-containing sugars

Carbon extension in peptidylnucleoside biosynthesis by radical SAM enzymes

Pyruvate Substitutions on Glycoconjugates

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