Complex Oxidation Chemistry in the Biosynthetic Pathways to Vancomycin/Teicoplanin Antibiotics

Widboom, Paul F.; Bruner, Steven D.

doi:10.1002/cbic.200900117

Cited by 15 publications

(9 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…arylomycin B‐C 16 ( 22 ), Figure 9). 74, 75 The side‐chain aryl ether in 21 is thought to arise from a one‐electron phenoxyl radical reaction on the two tyrosine side chains of a tripeptide precursor catalyzed by an iron‐based oxygenase 76. These cross‐links set the constrained architecture in 21 and 22 (Figure 9).…”

Section: Nonproteinogenic Amino Acid Residues In Nrp Frameworkmentioning

confidence: 99%

Metal‐Free Reduction of CO₂ with Hydroboranes: Two Efficient Pathways at Play for the Reduction of CO₂ to Methanol

Gomes

Blondiaux

Thuéry

et al. 2014

Chemistry A European J

152

View full text Add to dashboard Cite

Guanidines and amidines prove to be highly efficient metal-free catalysts for the reduction of CO2 to methanol with hydroboranes such as 9-borabicyclo[3.3.1]nonane (9-BBN) and catecholborane (catBH). Nitrogen bases, such as 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (Me-TBD), and 1,8-diazabicycloundec-7-ene (DBU), are active catalysts for this transformation and Me-TBD can catalyze the reduction of CO2 to methoxyborane at room temperature with TONs and TOFs of up to 648 and 33 h(-1) (25 °C), respectively. Formate HCOOBR2 and acetal H2C(OBR2)2 derivatives have been identified as reaction intermediates in the reduction of CO2 with R2BH, and the first C-H-bond formation is rate determining. Experimental and computational investigations show that TBD and Me-TBD follow distinct mechanisms. The N-H bond of TBD is reactive toward dehydrocoupling with 9-BBN and affords a novel frustrated Lewis pair (FLP) that can activate a CO2 molecule and form the stable adduct 2, which is the catalytically active species and can facilitate the hydride transfer from the boron to the carbon atoms. In contrast, Me-TBD promotes the reduction of CO2 through the activation of the hydroborane reagent. Detailed DFT calculations have shown that the computed energy barriers for the two mechanisms are consistent with the experimental findings and account for the reactivity of the different boron reductants.

show abstract

Section: Nonproteinogenic Amino Acid Residues In Nrp Frameworkmentioning

confidence: 99%

Metal‐Free Reduction of CO₂ with Hydroboranes: Two Efficient Pathways at Play for the Reduction of CO₂ to Methanol

Gomes

Blondiaux

Thuéry

et al. 2014

Chemistry A European J

152

View full text Add to dashboard Cite

show abstract

“…1). This a-hydroxy acid is the first intermediate in the pathway to the nonproteinogenic amino acid 4-hydroxyphenylglycine (HPG), which is known as an essential component of several glycopeptide antibiotics (Donadio et al 2005;Widboom and Bruner 2009). The formation of 4-hydroxymandelate is catalyzed by an iron(II)-dependent dioxygenase, and the corresponding enzyme, 4-hydroxymandelate synthase (HMS), is functionally related to 4-hydroxyphenylpyruvate dioxygenase (HPPD).…”

Section: Introductionmentioning

confidence: 99%

4-Hydroxyphenylglycine biosynthesis in Herpetosiphon aurantiacus: a case of gene duplication and catalytic divergence

et al. 2012

View full text Add to dashboard Cite

The nonproteinogenic amino acid 4-hydroxyphenylglycine (HPG) arises from the diversion of the tyrosine degradation pathway into secondary metabolism, and its biosynthesis requires a set of three enzymes. The gene cassette for HPG biosynthesis is widely spread in actinomycete bacteria, which incorporate the amino acid as a building block into various peptide antibiotics, but it has never been reported from another taxonomic group of eubacteria. A genome mining study has now revealed a putative HPG pathway in the predatory bacterium Herpetosiphon aurantiacus, which is phylogenetically distinct from Actinomycetes. Anomalies in the active center of one annotated key enzyme raised questions about the true product of this pathway, prompting an in vitro reconstitution attempt. This study confirmed the capability of H. aurantiacus for HPG production. Sequence analysis of the aberrant 4-hydroxymandelate synthase refines the existing model on the catalytic differentiation of iron(II)-dependent dioxygenases. Furthermore, we report a comprehensive analysis on the phylogeny of these enzymes, which sheds light on the evolution of paralogous gene sets and the ensuing metabolic diversity in a barely studied bacterium.

show abstract

“…From among these proteins, we will focus on DpgC, the first protein for which a crystal structure showing a substrate analog and O 2 bound to the enzyme was resolved [36–38] . DpgC is a hexameric crotonase oxygenase [39, 40] that plays a key role in the biosynthesis of dihydroxyphenylglycine (DPG), a non‐natural amino acid found in “antibiotics of last resort” such as vancomycin or teicoplanin [41] . In particular, DpgC catalyzes the cofactor‐independent oxidation of 3,5‐dihydroxyphenylacetyl‐CoA (DPA‐CoA) to 3,5‐dihydroxyphenyl‐glyoxylate (DPGX; Figure 1).…”

Section: Introductionmentioning

confidence: 99%

DpgC‐Catalyzed Peroxidation of 3,5‐Dihydroxyphenylacetyl‐CoA (DPA‐CoA): Insights into the Spin‐Forbidden Transition and Charge Transfer Mechanisms**

Ortega

Zanchet

Sanz-Sanz

et al. 2020

Chemistry A European J

View full text Add to dashboard Cite

Despite being a very strong oxidizing agent, most organic molecules are not oxidized in the presence of O2 at room temperature because O2 is a diradical whereas most organic molecules are closed‐shell. Oxidation then requires a change in the spin state of the system, which is forbidden according to non‐relativistic quantum theory. To overcome this limitation, oxygenases usually rely on metal or redox cofactors to catalyze the incorporation of, at least, one oxygen atom into an organic substrate. However, some oxygenases do not require any cofactor, and the detailed mechanism followed by these enzymes remains elusive. To fill this gap, here the mechanism for the enzymatic cofactor‐independent oxidation of 3,5‐dihydroxyphenylacetyl‐CoA (DPA‐CoA) is studied by combining multireference calculations on a model system with QM/MM calculations. Our results reveal that intersystem crossing takes place without requiring the previous protonation of molecular oxygen. The characterization of the electronic states reveals that electron transfer is concomitant with the triplet–singlet transition. The enzyme plays a passive role in promoting the intersystem crossing, although spontaneous reorganization of the water wire connecting the active site with the bulk presets the substrate for subsequent chemical transformations. The results show that the stabilization of the singlet radical‐pair between dioxygen and enolate is enough to promote spin‐forbidden reaction without the need for neither metal cofactors nor basic residues in the active site.

show abstract

Complex Oxidation Chemistry in the Biosynthetic Pathways to Vancomycin/Teicoplanin Antibiotics

Cited by 15 publications

References 68 publications

Metal‐Free Reduction of CO₂ with Hydroboranes: Two Efficient Pathways at Play for the Reduction of CO₂ to Methanol

Metal‐Free Reduction of CO₂ with Hydroboranes: Two Efficient Pathways at Play for the Reduction of CO₂ to Methanol

4-Hydroxyphenylglycine biosynthesis in Herpetosiphon aurantiacus: a case of gene duplication and catalytic divergence

DpgC‐Catalyzed Peroxidation of 3,5‐Dihydroxyphenylacetyl‐CoA (DPA‐CoA): Insights into the Spin‐Forbidden Transition and Charge Transfer Mechanisms**

Contact Info

Product

Resources

About

Complex Oxidation Chemistry in the Biosynthetic Pathways to Vancomycin/Teicoplanin Antibiotics

Cited by 15 publications

References 68 publications

Metal‐Free Reduction of CO2 with Hydroboranes: Two Efficient Pathways at Play for the Reduction of CO2 to Methanol

Metal‐Free Reduction of CO2 with Hydroboranes: Two Efficient Pathways at Play for the Reduction of CO2 to Methanol

4-Hydroxyphenylglycine biosynthesis in Herpetosiphon aurantiacus: a case of gene duplication and catalytic divergence

DpgC‐Catalyzed Peroxidation of 3,5‐Dihydroxyphenylacetyl‐CoA (DPA‐CoA): Insights into the Spin‐Forbidden Transition and Charge Transfer Mechanisms**

Contact Info

Product

Resources

About

Metal‐Free Reduction of CO₂ with Hydroboranes: Two Efficient Pathways at Play for the Reduction of CO₂ to Methanol

Metal‐Free Reduction of CO₂ with Hydroboranes: Two Efficient Pathways at Play for the Reduction of CO₂ to Methanol