Substrate‐Determined Diastereoselectivity in an Enzymatic Carboligation

Lehwald, Patrizia; Fuchs, Olga; Nafie, Laurence A.; Müller, Michael; Lüdeke, Steffen

doi:10.1002/cbic.201600202

Cited by 6 publications

(2 citation statements)

References 26 publications

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“…Example studies of high aromatic content proteins and model protein folds have appeared that utilize this property . In some cases, selective protein–DNA interaction studies or protein ligation studies are possible with VCD using the relative intensity and frequency resolution aspects of the IR to separate spectral contributions. − Complex protein systems, for example, keratin, have also been studied with VCD to sort out separate contributions to secondary structure . Glyco proteins can be studied to understand and isolate the peptide contributions since the carbohydrate contribution to VCD is weak. ,,, Little effort has been made to measure protein VCD beyond the amide I and II bands whose stronger transition dipoles can couple along the peptide chain and evidence secondary structure sensitivity.…”

Section: Protein Applicationsmentioning

confidence: 99%

Structure of Condensed Phase Peptides: Insights from Vibrational Circular Dichroism and Raman Optical Activity Techniques

2020

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Peptides and proteins are naturally chiral molecular systems so that sensing their structure and conformation with chirality-based spectral methods is an obvious and long-used diagnostic application. Extending chiroptical techniques to measurement of vibrational transitions, in the form of vibrational circular dichroism (VCD) and Raman optical activity (ROA), expands the number and types of excitations available that might provide structural insight and can provide an alternate and, in some cases, a more distinctive conformational probe. Since the dominant repeating structural element in peptides is the locally achiral amide group, VCD senses the polymeric structure through amide coupling, which is directly dependent on secondary structure. Determination of the type and relative contribution of these structural components through empirical correlation with spectral character has been the main application of VCD for peptides and proteins, although this is now reinforced by extensive theoretical modeling. Monitoring structural and conformational change induced by environmental perturbations provides another important application. More recently, VCD has been used to detect morphological variations in fibril states of aggregated peptides and proteins. ROA has parallel secondary structural sensitivities, with more applications for proteins than peptides, and has more sensitivity to local configuration and side chains. This review covers the range of peptide studies done with VCD and extends them to compare with example protein and ROA applications.

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Section: Protein Applicationsmentioning

confidence: 99%

Structure of Condensed Phase Peptides: Insights from Vibrational Circular Dichroism and Raman Optical Activity Techniques

2020

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“…The lack of the three‐dimensional structure hampers the possibility to effectively altering the catalytic properties of the biocatalyst. In this respect, information on the substrate binding‐site of YerE have been obtained from diastereochemical studies using a chiral ketone as the acceptor, i.e. 3‐methyl cyclohexanone, by means of vibrational circular dichroism (VCD).…”

Section: Acyloin‐type Reactionsmentioning

confidence: 99%

Building Up Quaternary Stereocenters Through Biocatalyzed Direct Insertion of Carbon Nucleophiles on Ketones

Gaggero

2019

Eur J Org Chem

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Quaternary stereocenters are privileged structural motifs, widely distributed in natural products and in pharmaceutically active compounds. Asymmetric methods for the efficient construction of these prominent frameworks are rapidly increasing. Biocatalysis represents an alternative to the existing methods of using hazardous metals and chemicals. Enzymes discussed in this mini-review involve thiamine-bisphosphate (ThDP)-dependent lyases, aldolases and hydroxynitrile lyases.[a] 7616 of CO 2 is transferred to the si face of an aldehyde acceptor to give an (R)-hydroxy ketone (Scheme 2). Scheme 2. Catalytic cycle of ThDP-dependent acyloin reaction.

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Identification of Kibdelomycin and Related Biosynthetic Gene Clusters and Characterization of the C‐Branching of Amycolose

Krug,

Bjarnesen,

Lanza

et al. 2024

Angewandte Chemie

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Many bacterial natural products contain C‐branched sugars, including components from the outer cell wall or antibiotically active metabolites. The enzymatic C‐branching of keto sugars leading to longer side chains (≥C2), is catalyzed by thiamine diphosphate (ThDP)‐dependent enzymes. Chiral tertiary α‐hydroxy ketones are formed in this process. The ThDP enzymes that catalyze C‐branching reactions belong to one of three enzymatic superfamilies: decarboxylases, transketolases, and α‐ketoacid dehydrogenases 2, but branching of keto sugars has only been demonstrated for decarboxylases. In this study, we showed that an α‐ketoacid dehydrogenase is responsible for C‐branching of the deoxyketo sugar amycolose in the biosynthesis of kibdelomycin in Kibdelosporangium sp. MA7385. In addition, we characterized an amino transferase in the same biosynthetic gene cluster (BGC) that accepts a sterically demanding tertiary α‐hydroxy ketone in a downstream reaction. Subsequently, we identified approximately 400 similar BGCs in silico, suggesting that there is a large diversity of possible ThDP‐dependent enzymes catalyzing the C‐branching of keto sugars and subsequent modifications.

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Substrate‐Determined Diastereoselectivity in an Enzymatic Carboligation

Cited by 6 publications

References 26 publications

Structure of Condensed Phase Peptides: Insights from Vibrational Circular Dichroism and Raman Optical Activity Techniques

Structure of Condensed Phase Peptides: Insights from Vibrational Circular Dichroism and Raman Optical Activity Techniques

Building Up Quaternary Stereocenters Through Biocatalyzed Direct Insertion of Carbon Nucleophiles on Ketones

Identification of Kibdelomycin and Related Biosynthetic Gene Clusters and Characterization of the C‐Branching of Amycolose

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