'Biosynthesis of hyalodendrin and didethiobis(methylthio)hyalodendrin, sulphur containing 2,5–dioxopiperazines of the 3S,6S Series

Maria I. Pita Boente, Gordon W. Kirby, Graham L. Patrick, David J. Robins

Research output: Contribution to journalArticle

Abstract

cyclo-(L-[4′-3H]Phe-L-[3-14C] Ser)8, a known biosynthetic precursor of the (3R,6R)-epidithiodioxopiperazine gliotoxin 4, was efficiently incorporated (42%), in Hyalodendron sp. (FSC-601) cultures, into the 3S,6S metabolite didethiobis(methylthio)hyalodendrin (DBH)7 without significant change in the 3H: 14C ratio. None of the three diastereoisomers of cyclo-(L-Phe-L-Ser) was incorporated into DBH to any significant extent. The 13C label from cyclo-(L-Phe-L-[3-13C]Ser) was located, in the expected site, in DBH by 13C NMR spectroscopy. Gliotoxin derived in Gliocladium virens from the doubly labelled precursor 8 was degraded to locate, in similar manner, the 14C label. The N-methyl derivative 16 of cyclo-(L-Phe-L–Ser) was not incorporated detectably into either gliotoxin or DBH. Radioactivity from the doubly labelled, linear dipeptides 17 and 18, possible precursors for the cyclodipeptide 8, was incorporated with moderate efficiency into gliotoxin. However, the 3H: 14C ratios for the dipeptides and the derived gliotoxin differed substantially, indicating that the peptides had undergone cleavage in the fungus before incorporation.
Original languageEnglish
Pages (from-to)1283-1290
Number of pages8
JournalJournal of the Chemical Society, Perkin Transactions 1
Issue number5
Publication statusPublished - 1991

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Gliotoxin
Biosynthesis
Sulfur
Dipeptides
Labels
Radioactivity
Metabolites
Fungi
Nuclear magnetic resonance spectroscopy
hyalodendrin
Derivatives
Peptides

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@article{65ab45b43bdd45cd9412bf79bde630cf,
title = "'Biosynthesis of hyalodendrin and didethiobis(methylthio)hyalodendrin, sulphur containing 2,5–dioxopiperazines of the 3S,6S Series",
abstract = "cyclo-(L-[4′-3H]Phe-L-[3-14C] Ser)8, a known biosynthetic precursor of the (3R,6R)-epidithiodioxopiperazine gliotoxin 4, was efficiently incorporated (42{\%}), in Hyalodendron sp. (FSC-601) cultures, into the 3S,6S metabolite didethiobis(methylthio)hyalodendrin (DBH)7 without significant change in the 3H: 14C ratio. None of the three diastereoisomers of cyclo-(L-Phe-L-Ser) was incorporated into DBH to any significant extent. The 13C label from cyclo-(L-Phe-L-[3-13C]Ser) was located, in the expected site, in DBH by 13C NMR spectroscopy. Gliotoxin derived in Gliocladium virens from the doubly labelled precursor 8 was degraded to locate, in similar manner, the 14C label. The N-methyl derivative 16 of cyclo-(L-Phe-L–Ser) was not incorporated detectably into either gliotoxin or DBH. Radioactivity from the doubly labelled, linear dipeptides 17 and 18, possible precursors for the cyclodipeptide 8, was incorporated with moderate efficiency into gliotoxin. However, the 3H: 14C ratios for the dipeptides and the derived gliotoxin differed substantially, indicating that the peptides had undergone cleavage in the fungus before incorporation.",
author = "{Pita Boente}, {Maria I.} and Kirby, {Gordon W.} and Patrick, {Graham L.} and Robins, {David J.}",
year = "1991",
language = "English",
pages = "1283--1290",
journal = "Journal of the Chemical Society, Perkin Transactions 1",
issn = "2050-8255",
publisher = "Royal Society of Chemistry",
number = "5",

}

'Biosynthesis of hyalodendrin and didethiobis(methylthio)hyalodendrin, sulphur containing 2,5–dioxopiperazines of the 3S,6S Series. / Pita Boente, Maria I.; Kirby, Gordon W.; Patrick, Graham L.; Robins, David J.

In: Journal of the Chemical Society, Perkin Transactions 1, No. 5, 1991, p. 1283-1290.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 'Biosynthesis of hyalodendrin and didethiobis(methylthio)hyalodendrin, sulphur containing 2,5–dioxopiperazines of the 3S,6S Series

AU - Pita Boente, Maria I.

AU - Kirby, Gordon W.

AU - Patrick, Graham L.

AU - Robins, David J.

PY - 1991

Y1 - 1991

N2 - cyclo-(L-[4′-3H]Phe-L-[3-14C] Ser)8, a known biosynthetic precursor of the (3R,6R)-epidithiodioxopiperazine gliotoxin 4, was efficiently incorporated (42%), in Hyalodendron sp. (FSC-601) cultures, into the 3S,6S metabolite didethiobis(methylthio)hyalodendrin (DBH)7 without significant change in the 3H: 14C ratio. None of the three diastereoisomers of cyclo-(L-Phe-L-Ser) was incorporated into DBH to any significant extent. The 13C label from cyclo-(L-Phe-L-[3-13C]Ser) was located, in the expected site, in DBH by 13C NMR spectroscopy. Gliotoxin derived in Gliocladium virens from the doubly labelled precursor 8 was degraded to locate, in similar manner, the 14C label. The N-methyl derivative 16 of cyclo-(L-Phe-L–Ser) was not incorporated detectably into either gliotoxin or DBH. Radioactivity from the doubly labelled, linear dipeptides 17 and 18, possible precursors for the cyclodipeptide 8, was incorporated with moderate efficiency into gliotoxin. However, the 3H: 14C ratios for the dipeptides and the derived gliotoxin differed substantially, indicating that the peptides had undergone cleavage in the fungus before incorporation.

AB - cyclo-(L-[4′-3H]Phe-L-[3-14C] Ser)8, a known biosynthetic precursor of the (3R,6R)-epidithiodioxopiperazine gliotoxin 4, was efficiently incorporated (42%), in Hyalodendron sp. (FSC-601) cultures, into the 3S,6S metabolite didethiobis(methylthio)hyalodendrin (DBH)7 without significant change in the 3H: 14C ratio. None of the three diastereoisomers of cyclo-(L-Phe-L-Ser) was incorporated into DBH to any significant extent. The 13C label from cyclo-(L-Phe-L-[3-13C]Ser) was located, in the expected site, in DBH by 13C NMR spectroscopy. Gliotoxin derived in Gliocladium virens from the doubly labelled precursor 8 was degraded to locate, in similar manner, the 14C label. The N-methyl derivative 16 of cyclo-(L-Phe-L–Ser) was not incorporated detectably into either gliotoxin or DBH. Radioactivity from the doubly labelled, linear dipeptides 17 and 18, possible precursors for the cyclodipeptide 8, was incorporated with moderate efficiency into gliotoxin. However, the 3H: 14C ratios for the dipeptides and the derived gliotoxin differed substantially, indicating that the peptides had undergone cleavage in the fungus before incorporation.

M3 - Article

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