The identification of (3R, 4S)-5-fluoro-5-deoxy-D-ribulose-1-phosphate as an intermediate in fluorometabolite biosynthesis in Streptomyces cattleya

Mayca Onega, Ryan P. McGlinchey, Hai Deng, John T. G. Hamilton, David O'hagan (Corresponding Author)

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

(3R,4S)-5-Fluoro-5-deoxy-d-ribulose-1-phosphate (5-FDRulP) has been identified as the third fluorinated intermediate on the biosynthetic pathway to fluoroacetate and 4-fluorothreonine in Streptomyces cattleya. 5-FDRulP is generated after formation of 5′-fluoro-5′-deoxyadenosine (5′-FDA) and then phosphorolysis of 5′-FDA to 5-fluoro-5-deoxy-d-ribose-1-phosphate (5-FDRP) by the action of a purine nucleoside phosphorylase. An isomerase mediates the conversion of 5-FDRP to 5-FDRulP. The identity of the (3R,4S) diastereoisomer of 5-FDRulP was established by comparative 19F{1H} NMR studies whereby 5-FDRulP that accumulated in a cell free extract of S. cattleya, was treated with a phytase to generate the non-phosphorylated sugar, 5-fluoro-5-deoxy-d-ribulose (5-FDRul). This S. cattleya product was compared to the product of an in-vitro biotransformation where separately 5-fluoro-5-deoxy-d-ribose and 5-fluoro-5-deoxy-d-xylose were converted to 5-fluoro-5-deoxy-d-ribulose and 5-fluoro-5-deoxy-d-xylulose respectively by the action of glucose isomerase. It was demonstrated that 5-fluoro-5-deoxy-d-ribose gave the identical diastereoisomer to that observed from 5-FDRulP.

Original languageEnglish
Pages (from-to)375-385
Number of pages11
JournalBioorganic Chemistry
Volume35
Issue number5
Early online date14 Jun 2007
DOIs
Publication statusPublished - Oct 2007

Fingerprint

Biosynthesis
Streptomyces
Phosphates
Ribose
xylose isomerase
Fluoroacetates
Xylulose
Purine-Nucleoside Phosphorylase
6-Phytase
Isomerases
ribulose
Xylose
Biosynthetic Pathways
Biotransformation
Cell Extracts
Sugars
Nuclear magnetic resonance

Keywords

  • Streptomyces cattleya
  • 5-Fluoro-5-deoxy-d-ribulose-1-phosphate
  • Fluoroacetate4-Fluorothreonine
  • Fluorinase
  • Glucose isomerase

Cite this

The identification of (3R, 4S)-5-fluoro-5-deoxy-D-ribulose-1-phosphate as an intermediate in fluorometabolite biosynthesis in Streptomyces cattleya. / Onega, Mayca; McGlinchey, Ryan P.; Deng, Hai; Hamilton, John T. G.; O'hagan, David (Corresponding Author).

In: Bioorganic Chemistry, Vol. 35, No. 5, 10.2007, p. 375-385.

Research output: Contribution to journalArticle

Onega, Mayca ; McGlinchey, Ryan P. ; Deng, Hai ; Hamilton, John T. G. ; O'hagan, David. / The identification of (3R, 4S)-5-fluoro-5-deoxy-D-ribulose-1-phosphate as an intermediate in fluorometabolite biosynthesis in Streptomyces cattleya. In: Bioorganic Chemistry. 2007 ; Vol. 35, No. 5. pp. 375-385.
@article{9a3f0b64a18d4dc794073caf76947cfa,
title = "The identification of (3R, 4S)-5-fluoro-5-deoxy-D-ribulose-1-phosphate as an intermediate in fluorometabolite biosynthesis in Streptomyces cattleya",
abstract = "(3R,4S)-5-Fluoro-5-deoxy-d-ribulose-1-phosphate (5-FDRulP) has been identified as the third fluorinated intermediate on the biosynthetic pathway to fluoroacetate and 4-fluorothreonine in Streptomyces cattleya. 5-FDRulP is generated after formation of 5′-fluoro-5′-deoxyadenosine (5′-FDA) and then phosphorolysis of 5′-FDA to 5-fluoro-5-deoxy-d-ribose-1-phosphate (5-FDRP) by the action of a purine nucleoside phosphorylase. An isomerase mediates the conversion of 5-FDRP to 5-FDRulP. The identity of the (3R,4S) diastereoisomer of 5-FDRulP was established by comparative 19F{1H} NMR studies whereby 5-FDRulP that accumulated in a cell free extract of S. cattleya, was treated with a phytase to generate the non-phosphorylated sugar, 5-fluoro-5-deoxy-d-ribulose (5-FDRul). This S. cattleya product was compared to the product of an in-vitro biotransformation where separately 5-fluoro-5-deoxy-d-ribose and 5-fluoro-5-deoxy-d-xylose were converted to 5-fluoro-5-deoxy-d-ribulose and 5-fluoro-5-deoxy-d-xylulose respectively by the action of glucose isomerase. It was demonstrated that 5-fluoro-5-deoxy-d-ribose gave the identical diastereoisomer to that observed from 5-FDRulP.",
keywords = "Streptomyces cattleya, 5-Fluoro-5-deoxy-d-ribulose-1-phosphate, Fluoroacetate4-Fluorothreonine, Fluorinase, Glucose isomerase",
author = "Mayca Onega and McGlinchey, {Ryan P.} and Hai Deng and Hamilton, {John T. G.} and David O'hagan",
note = "We are grateful to the EPSRC for a Studenship (MO), GSK and the EPSRC for a CASE Studentship (RMcG) and the BBSRC for a grant funding (HD).",
year = "2007",
month = "10",
doi = "10.1016/j.bioorg.2007.04.001",
language = "English",
volume = "35",
pages = "375--385",
journal = "Bioorganic Chemistry",
issn = "0045-2068",
publisher = "Academic Press Inc.",
number = "5",

}

TY - JOUR

T1 - The identification of (3R, 4S)-5-fluoro-5-deoxy-D-ribulose-1-phosphate as an intermediate in fluorometabolite biosynthesis in Streptomyces cattleya

AU - Onega, Mayca

AU - McGlinchey, Ryan P.

AU - Deng, Hai

AU - Hamilton, John T. G.

AU - O'hagan, David

N1 - We are grateful to the EPSRC for a Studenship (MO), GSK and the EPSRC for a CASE Studentship (RMcG) and the BBSRC for a grant funding (HD).

PY - 2007/10

Y1 - 2007/10

N2 - (3R,4S)-5-Fluoro-5-deoxy-d-ribulose-1-phosphate (5-FDRulP) has been identified as the third fluorinated intermediate on the biosynthetic pathway to fluoroacetate and 4-fluorothreonine in Streptomyces cattleya. 5-FDRulP is generated after formation of 5′-fluoro-5′-deoxyadenosine (5′-FDA) and then phosphorolysis of 5′-FDA to 5-fluoro-5-deoxy-d-ribose-1-phosphate (5-FDRP) by the action of a purine nucleoside phosphorylase. An isomerase mediates the conversion of 5-FDRP to 5-FDRulP. The identity of the (3R,4S) diastereoisomer of 5-FDRulP was established by comparative 19F{1H} NMR studies whereby 5-FDRulP that accumulated in a cell free extract of S. cattleya, was treated with a phytase to generate the non-phosphorylated sugar, 5-fluoro-5-deoxy-d-ribulose (5-FDRul). This S. cattleya product was compared to the product of an in-vitro biotransformation where separately 5-fluoro-5-deoxy-d-ribose and 5-fluoro-5-deoxy-d-xylose were converted to 5-fluoro-5-deoxy-d-ribulose and 5-fluoro-5-deoxy-d-xylulose respectively by the action of glucose isomerase. It was demonstrated that 5-fluoro-5-deoxy-d-ribose gave the identical diastereoisomer to that observed from 5-FDRulP.

AB - (3R,4S)-5-Fluoro-5-deoxy-d-ribulose-1-phosphate (5-FDRulP) has been identified as the third fluorinated intermediate on the biosynthetic pathway to fluoroacetate and 4-fluorothreonine in Streptomyces cattleya. 5-FDRulP is generated after formation of 5′-fluoro-5′-deoxyadenosine (5′-FDA) and then phosphorolysis of 5′-FDA to 5-fluoro-5-deoxy-d-ribose-1-phosphate (5-FDRP) by the action of a purine nucleoside phosphorylase. An isomerase mediates the conversion of 5-FDRP to 5-FDRulP. The identity of the (3R,4S) diastereoisomer of 5-FDRulP was established by comparative 19F{1H} NMR studies whereby 5-FDRulP that accumulated in a cell free extract of S. cattleya, was treated with a phytase to generate the non-phosphorylated sugar, 5-fluoro-5-deoxy-d-ribulose (5-FDRul). This S. cattleya product was compared to the product of an in-vitro biotransformation where separately 5-fluoro-5-deoxy-d-ribose and 5-fluoro-5-deoxy-d-xylose were converted to 5-fluoro-5-deoxy-d-ribulose and 5-fluoro-5-deoxy-d-xylulose respectively by the action of glucose isomerase. It was demonstrated that 5-fluoro-5-deoxy-d-ribose gave the identical diastereoisomer to that observed from 5-FDRulP.

KW - Streptomyces cattleya

KW - 5-Fluoro-5-deoxy-d-ribulose-1-phosphate

KW - Fluoroacetate4-Fluorothreonine

KW - Fluorinase

KW - Glucose isomerase

U2 - 10.1016/j.bioorg.2007.04.001

DO - 10.1016/j.bioorg.2007.04.001

M3 - Article

VL - 35

SP - 375

EP - 385

JO - Bioorganic Chemistry

JF - Bioorganic Chemistry

SN - 0045-2068

IS - 5

ER -