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An unusual carbon-carbon bond cleavage reaction during phosphinothricin biosynthesis.

Cicchillo RM, Zhang H, Blodgett JA, Whitteck JT, Li G, Nair SK, van der Donk WA, Metcalf WW - Nature (2009)

Bottom Line: Natural products containing phosphorus-carbon bonds have found widespread use in medicine and agriculture.In contrast to most other members of this family, the oxidative consumption of HEP does not require additional cofactors or the input of exogenous electrons.The current study expands the scope of reactions catalysed by the 2-His-1-carboxylate mononuclear non-haem iron family of enzymes.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.

ABSTRACT
Natural products containing phosphorus-carbon bonds have found widespread use in medicine and agriculture. One such compound, phosphinothricin tripeptide, contains the unusual amino acid phosphinothricin attached to two alanine residues. Synthetic phosphinothricin (glufosinate) is a component of two top-selling herbicides (Basta and Liberty), and is widely used with resistant transgenic crops including corn, cotton and canola. Recent genetic and biochemical studies showed that during phosphinothricin tripeptide biosynthesis 2-hydroxyethylphosphonate (HEP) is converted to hydroxymethylphosphonate (HMP). Here we report the in vitro reconstitution of this unprecedented C(sp(3))-C(sp(3)) bond cleavage reaction and X-ray crystal structures of the enzyme. The protein is a mononuclear non-haem iron(ii)-dependent dioxygenase that converts HEP to HMP and formate. In contrast to most other members of this family, the oxidative consumption of HEP does not require additional cofactors or the input of exogenous electrons. The current study expands the scope of reactions catalysed by the 2-His-1-carboxylate mononuclear non-haem iron family of enzymes.

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Related in: MedlinePlus

Structure of PTT and the reaction catalyzed by HEPDThe biosyntheses of the commercial herbicide phosphinothricin (boxed in the PTT structure) and the clinically used antibiotic fosfomycin share several early steps starting with phosphoenolpyruvate before the pathways diverge after formation of HEP.2,20 HEPD catalyzes the unprecedented conversion of HEP to HMP (for the steps from HMP to PTT, see Supplementary Fig. 8). The structurally related enzyme HppE converts HPP to fosfomycin21.
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Figure 1: Structure of PTT and the reaction catalyzed by HEPDThe biosyntheses of the commercial herbicide phosphinothricin (boxed in the PTT structure) and the clinically used antibiotic fosfomycin share several early steps starting with phosphoenolpyruvate before the pathways diverge after formation of HEP.2,20 HEPD catalyzes the unprecedented conversion of HEP to HMP (for the steps from HMP to PTT, see Supplementary Fig. 8). The structurally related enzyme HppE converts HPP to fosfomycin21.

Mentions: Natural products containing phosphorus-carbon bonds have found widespread use in medicine and agriculture1. One such compound, phosphinothricin tripeptide (PTT), contains the unusual amino acid phosphinothricin (PT) attached to two alanine residues (Fig. 1). Synthetic PT (glufosinate) is a component of two top-selling herbicides (Basta® and Liberty®), and is widely used with resistant transgenic crops including corn, cotton and canola. Recent genetic and biochemical studies showed that during PTT biosynthesis 2-hydroxyethylphosphonate (HEP) is converted to hydroxymethylphosphonate (HMP) (Fig. 1)2. Reported here are the in vitro reconstitution of this unprecedented C(sp3)-C(sp3) bond cleavage reaction and X-ray crystal structures of the enzyme. The protein is a mononuclear non-heme iron(II)-dependent dioxygenase that converts HEP to HMP and formate. In contrast to most other members of this family, the oxidative consumption of HEP does not require additional cofactors or the input of exogenous electrons. The current study expands the scope of reactions catalyzed by the 2-His-1-carboxylate mononuclear non-heme iron family of enzymes.


An unusual carbon-carbon bond cleavage reaction during phosphinothricin biosynthesis.

Cicchillo RM, Zhang H, Blodgett JA, Whitteck JT, Li G, Nair SK, van der Donk WA, Metcalf WW - Nature (2009)

Structure of PTT and the reaction catalyzed by HEPDThe biosyntheses of the commercial herbicide phosphinothricin (boxed in the PTT structure) and the clinically used antibiotic fosfomycin share several early steps starting with phosphoenolpyruvate before the pathways diverge after formation of HEP.2,20 HEPD catalyzes the unprecedented conversion of HEP to HMP (for the steps from HMP to PTT, see Supplementary Fig. 8). The structurally related enzyme HppE converts HPP to fosfomycin21.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2874955&req=5

Figure 1: Structure of PTT and the reaction catalyzed by HEPDThe biosyntheses of the commercial herbicide phosphinothricin (boxed in the PTT structure) and the clinically used antibiotic fosfomycin share several early steps starting with phosphoenolpyruvate before the pathways diverge after formation of HEP.2,20 HEPD catalyzes the unprecedented conversion of HEP to HMP (for the steps from HMP to PTT, see Supplementary Fig. 8). The structurally related enzyme HppE converts HPP to fosfomycin21.
Mentions: Natural products containing phosphorus-carbon bonds have found widespread use in medicine and agriculture1. One such compound, phosphinothricin tripeptide (PTT), contains the unusual amino acid phosphinothricin (PT) attached to two alanine residues (Fig. 1). Synthetic PT (glufosinate) is a component of two top-selling herbicides (Basta® and Liberty®), and is widely used with resistant transgenic crops including corn, cotton and canola. Recent genetic and biochemical studies showed that during PTT biosynthesis 2-hydroxyethylphosphonate (HEP) is converted to hydroxymethylphosphonate (HMP) (Fig. 1)2. Reported here are the in vitro reconstitution of this unprecedented C(sp3)-C(sp3) bond cleavage reaction and X-ray crystal structures of the enzyme. The protein is a mononuclear non-heme iron(II)-dependent dioxygenase that converts HEP to HMP and formate. In contrast to most other members of this family, the oxidative consumption of HEP does not require additional cofactors or the input of exogenous electrons. The current study expands the scope of reactions catalyzed by the 2-His-1-carboxylate mononuclear non-heme iron family of enzymes.

Bottom Line: Natural products containing phosphorus-carbon bonds have found widespread use in medicine and agriculture.In contrast to most other members of this family, the oxidative consumption of HEP does not require additional cofactors or the input of exogenous electrons.The current study expands the scope of reactions catalysed by the 2-His-1-carboxylate mononuclear non-haem iron family of enzymes.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.

ABSTRACT
Natural products containing phosphorus-carbon bonds have found widespread use in medicine and agriculture. One such compound, phosphinothricin tripeptide, contains the unusual amino acid phosphinothricin attached to two alanine residues. Synthetic phosphinothricin (glufosinate) is a component of two top-selling herbicides (Basta and Liberty), and is widely used with resistant transgenic crops including corn, cotton and canola. Recent genetic and biochemical studies showed that during phosphinothricin tripeptide biosynthesis 2-hydroxyethylphosphonate (HEP) is converted to hydroxymethylphosphonate (HMP). Here we report the in vitro reconstitution of this unprecedented C(sp(3))-C(sp(3)) bond cleavage reaction and X-ray crystal structures of the enzyme. The protein is a mononuclear non-haem iron(ii)-dependent dioxygenase that converts HEP to HMP and formate. In contrast to most other members of this family, the oxidative consumption of HEP does not require additional cofactors or the input of exogenous electrons. The current study expands the scope of reactions catalysed by the 2-His-1-carboxylate mononuclear non-haem iron family of enzymes.

Show MeSH
Related in: MedlinePlus