Biosynthesis of penicillin G from<scp>D</scp>- and<scp>L</scp>-[<sup>14</sup>C]- and [α-<sup>3</sup>H]-valine

Bycroft, Barrie W.; Wels, Colin M.; Corbett, K.; Maloney, Adrian P.; Lowe, David

doi:10.1039/c39750000923

Cited by 12 publications

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“…Likewise the antibiotic penicillin has three stereocenters yielding eight possible stereoisomers, yet only the (2 S ,5 R ,6 R )-diastereomer has significant antibacterial activity, and chloramphenicol, an antibiotic for the treatment of meningitis, cholera, and typhoid fever, shows only the ( R , R )-diastereomer is active (Figure ). In addition to compound activity, determining the correct structure, including the correct stereochemistry, is essential in protecting intellectual property and avoiding costly patent disputes. , …”

Section: Introductionmentioning

confidence: 99%

“…2 In addition to compound activity, determining the correct structure, including the correct stereochemistry, is essential in protecting intellectual property and avoiding costly patent disputes. 3,4 Two powerful technologies for determining the stereochemistry of diastereomers include single crystal X-ray and NMR spectroscopy. While X-ray crystallography can unequivocally establish the stereochemistry of diastereomers, the technology requires sufficient quantity, purity, and solubility of the material as well as the time and resources to grow a diffraction quality crystal.…”

Section: ■ Introductionmentioning

confidence: 99%

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DiCE: Diastereomeric in Silico Chiral Elucidation, Expanded DP4 Probability Theory Method for Diastereomer and Structural Assignment

2018

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NMR chemical shift prediction at the B3LYP/cc-pVDZ level of theory was used to develop a highly accurate probability theory algorithm for the determination of the stereochemistry of diastereomers as well as the regiochemistry. DFT-GIAO calculations were performed for each conformer using geometry optimization and a CPCM solvent model. Boltzmann averaged shielding constants were converted to chemical shifts for H andC, using the generalized linear scaling terms determined in four different solvents for H andC and extended to N in DMSO. The probability theory algorithm, D iCE, was based on the DP4 method and developed forH, C, andN NMR using individual and combined probability data. The chemical shift calculation errors were fitted to a Student's t-distribution for H andC and a normal distribution for N. The application yielded a high accuracy for structural assignment with a low computational cost.

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Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

DiCE: Diastereomeric in Silico Chiral Elucidation, Expanded DP4 Probability Theory Method for Diastereomer and Structural Assignment

2018

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“…Since this tripeptide is accompanied in the mycelium of C. acremonium by a related peptide containing a residue of 8-hydroxyvaline (Loder & Abraham, 1971a), the question arises of whether oxidation at the l-carbon atom of a valine residue precedes closure of the thiazolidine ring. Adriaens et al (1975a) and Bycroft et al (1975) have shown by experiments with DL-[2-3H]valine, 4,valine and D-[2-3H]valine respectively that D-valine is not incorporated directly into penicillin produced by P. chrysogenum, but only after epimerization to L-valine, and that no 3H migration from C-3 to C-2 of the valine occurs during this process. These results are consistent with the synthesis of the LLD tripeptide from L-valine, but not from the D isomer, in C. acremonium (Abraham, 1974).…”

Section: Discussionmentioning

confidence: 99%

Synthesis of δ-(α-aminoadipyl)cysteinylvaline and its role in penicillin biosynthesis

Fawcett¹,

Usher²,

Huddleston³

et al. 1976

Biochemical Journal

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1. The stereoisomers of delta-(alpha-aminoadipyl)-L-cysteinylvaline (LLD, LLL and DLD) were synthesized from valine labelled with 3H in its methyl groups or in the alpha position. L-Cysteinyl-D-[4,4'-3H]valine was also synthesized. 2. 3H was incorporated into a compound that behaved like penicillin N when the LLD tripeptide containing either a methyl- or an alpha-labelled valine residue was incubated with a cell-free system prepared by lysis of protoplasts of Cephalosporium acremonium. 3. Incorporation was not observed under these conditions from the labelled all-L- or DLD-tripeptide, from L-cysteinyl-D-[4,4'-3H]valine, or of Penicillium chrysogenum appeared to be the LLD isomer, like that from C. acremonium. 5. These findings are discussed in relation to penicillin biosynthesis.

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“…Neither the tritium label from 0-nor that from L- [2-3 H] valine is incorporated into penicillin by P. chrysogenum cells (Bycroft et at., 1975b;Adriaens et at., 1975), suggesting that the o-isomer is not a direct precursor of penicillin. The loss of label from the IX-position of the L-isomer was to be expected with the inversion of configuration in the final product.…”

Section: Incorporation Of Valine and Cyst(e)ine Into Penicillins And mentioning

confidence: 99%

Penicillium and Acremonium

Peberdy¹

1987

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v Foreword Biotechnology is a word that was originally coined to describe the new processes which could be derived from our ability to manipulate, in vitro, the genetic material common to all organisms. I t has now become a generic term encompassing all "applications" of living systems, including the more traditional fermentation and agricultural industries. Recombinant DNA technology has opened up new opportunities for the exploitation of microorganisms and animal and plant cells as producers or modifiers of chemical and biological products.This series of handbooks deals exclusively with microorganisms which are at the forefront of the new technologies and brings together in each of its volumes the background information necessary to appreciate the historical development of the organisms making up a particular genus, the degree to which molecular biology has opened up new opportunities, and the place they occupy in today's biotechnology industry. Our aim was to make this primarily a practical approach, with emphasis on methodology, combining for the first time information which has largely been spread across a wide literature base or only touched upon briefly in review articles. Each handbook should provide the reader with a source text, from which the importance of the genus to his or her work can be identified, and a practical guide to the handling and exploitation of the organisms included.It is perhaps apt that Volume I of the series should deal with a group of organisms involved in producing chemicals which have dominated the fermentation and pharmaceutical industries for the past forty years-the antibiotics. In terms of the degree to which molecular biology has made an impact on this genus to date, it is clear that the major rewards are still to come.

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Biosynthesis of penicillin G fromD- andL-[¹⁴C]- and [α-³H]-valine

Abstract: Excellent incorporations of both D-[l-14C]-and L-[ U-14C]-valine into penicillin G by a high producing strain of Pencillium chrysogenum is reported ; the label from ~-[a-~H]-valine is not incorporated.

Cited by 12 publications

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DiCE: Diastereomeric in Silico Chiral Elucidation, Expanded DP4 Probability Theory Method for Diastereomer and Structural Assignment

DiCE: Diastereomeric in Silico Chiral Elucidation, Expanded DP4 Probability Theory Method for Diastereomer and Structural Assignment

Synthesis of δ-(α-aminoadipyl)cysteinylvaline and its role in penicillin biosynthesis

Penicillium and Acremonium

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Biosynthesis of penicillin G fromD- andL-[14C]- and [α-3H]-valine

Abstract: Excellent incorporations of both D-[l-14C]-and L-[ U-14C]-valine into penicillin G by a high producing strain of Pencillium chrysogenum is reported ; the label from ~-[a-~H]-valine is not incorporated.

Cited by 12 publications

References 0 publications

DiCE: Diastereomeric in Silico Chiral Elucidation, Expanded DP4 Probability Theory Method for Diastereomer and Structural Assignment

DiCE: Diastereomeric in Silico Chiral Elucidation, Expanded DP4 Probability Theory Method for Diastereomer and Structural Assignment

Synthesis of δ-(α-aminoadipyl)cysteinylvaline and its role in penicillin biosynthesis

Penicillium and Acremonium

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Biosynthesis of penicillin G fromD- andL-[¹⁴C]- and [α-³H]-valine