Identification of a fluorometabolite from Streptomyces sp. MA37: (2R,3S,4S)-5-Fluoro-2,3,4-trihydroxypentanoic acid

Long Ma; Axel Bartholome; Ming Him Tong; Zhiwei Qin; Yi Yu; Thomas Shepherd; Kwaku Kyeremeh; Hai Deng; David O’Hagan

doi:10.1039/C4SC03540B

Identification of a fluorometabolite from Streptomyces sp. MA37: (2R,3S,4S)-5-Fluoro-2,3,4-trihydroxypentanoic acid

Long Ma, Axel Bartholome, Ming Him Tong, Zhiwei Qin, Yi Yu, Thomas Shepherd, Kwaku Kyeremeh, Hai Deng^* (Corresponding Author), David O’Hagan (Corresponding Author)

^*Corresponding author for this work

Chemistry

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Abstract

(2R3S4S)-5-Fluoro-2,3,4-trihydroxypentanoic acid (5-FHPA) has been discovered as a new fluorometabolite in the soil bacterium Streptomyces sp. MA37. Exogenous addition of 5-fluoro-5-deoxy-D-ribose (5-FDR) into the cell free extract of MA37 demonstrated that 5-FDR was an intermediate to a range of unidentified fluorometabolites, distinct from fluoroacetate (FAc) and 4-fluorothreonine (4-FT). Bioinformatics analysis allowed identification of a gene cluster (fdr), encoding a pathway to the biosynthesis of 5-FHPA. Over-expression and in vitro assay of FdrC indicated that FdrC is a NAD+ dependent dehydrogenase responsible for oxidation of 5-FDR into 5-fluoro-5-deoxy-lactone, followed by hydrolysis to 5-FHPA. The identity of 5-FHPA in the fermentation broth was confirmed by synthesis of a reference compound and then co-correlation by 19F-NMR and GC-MS analysis. The occurrence of 5-FHPA proves the existence of a new fluorometabolite pathway.

Original language	English
Pages (from-to)	1414-1419
Number of pages	6
Journal	Chemical Science
Volume	6
Issue number	2
Early online date	3 Dec 2014
DOIs	https://doi.org/10.1039/C4SC03540B
Publication status	Published - 2015

Bibliographical note

Acknowledgements
DOH thanks EPSRC and the ERC for nancial support. He also acknowledges the Royal Society for a Wolfson Merit Award. KK and HD thank the Leverhulme Trust; Royal Society Africa Award (AA090088).

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Identification of a fluorometabolite from Streptomyces sp. MA37: (2R,3S,4S)-5-Fluoro-2,3,4-trihydroxypentanoic acid
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Hai Deng
- School of Natural & Computing Sciences, Chemistry - Personal Chair
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title = "Identification of a fluorometabolite from Streptomyces sp. MA37: (2R,3S,4S)-5-Fluoro-2,3,4-trihydroxypentanoic acid",

abstract = "(2R3S4S)-5-Fluoro-2,3,4-trihydroxypentanoic acid (5-FHPA) has been discovered as a new fluorometabolite in the soil bacterium Streptomyces sp. MA37. Exogenous addition of 5-fluoro-5-deoxy-D-ribose (5-FDR) into the cell free extract of MA37 demonstrated that 5-FDR was an intermediate to a range of unidentified fluorometabolites, distinct from fluoroacetate (FAc) and 4-fluorothreonine (4-FT). Bioinformatics analysis allowed identification of a gene cluster (fdr), encoding a pathway to the biosynthesis of 5-FHPA. Over-expression and in vitro assay of FdrC indicated that FdrC is a NAD+ dependent dehydrogenase responsible for oxidation of 5-FDR into 5-fluoro-5-deoxy-lactone, followed by hydrolysis to 5-FHPA. The identity of 5-FHPA in the fermentation broth was confirmed by synthesis of a reference compound and then co-correlation by 19F-NMR and GC-MS analysis. The occurrence of 5-FHPA proves the existence of a new fluorometabolite pathway.",

author = "Long Ma and Axel Bartholome and Tong, {Ming Him} and Zhiwei Qin and Yi Yu and Thomas Shepherd and Kwaku Kyeremeh and Hai Deng and David O{\textquoteright}Hagan",

note = "Acknowledgements DOH thanks EPSRC and the ERC for nancial support. He also acknowledges the Royal Society for a Wolfson Merit Award. KK and HD thank the Leverhulme Trust; Royal Society Africa Award (AA090088).",

year = "2015",

doi = "10.1039/C4SC03540B",

language = "English",

volume = "6",

pages = "1414--1419",

journal = "Chemical Science",

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T1 - Identification of a fluorometabolite from Streptomyces sp. MA37: (2R,3S,4S)-5-Fluoro-2,3,4-trihydroxypentanoic acid

AU - Ma, Long

AU - Bartholome, Axel

AU - Tong, Ming Him

AU - Qin, Zhiwei

AU - Yu, Yi

AU - Shepherd, Thomas

AU - Kyeremeh, Kwaku

AU - Deng, Hai

AU - O’Hagan, David

N1 - Acknowledgements DOH thanks EPSRC and the ERC for nancial support. He also acknowledges the Royal Society for a Wolfson Merit Award. KK and HD thank the Leverhulme Trust; Royal Society Africa Award (AA090088).

PY - 2015

Y1 - 2015

N2 - (2R3S4S)-5-Fluoro-2,3,4-trihydroxypentanoic acid (5-FHPA) has been discovered as a new fluorometabolite in the soil bacterium Streptomyces sp. MA37. Exogenous addition of 5-fluoro-5-deoxy-D-ribose (5-FDR) into the cell free extract of MA37 demonstrated that 5-FDR was an intermediate to a range of unidentified fluorometabolites, distinct from fluoroacetate (FAc) and 4-fluorothreonine (4-FT). Bioinformatics analysis allowed identification of a gene cluster (fdr), encoding a pathway to the biosynthesis of 5-FHPA. Over-expression and in vitro assay of FdrC indicated that FdrC is a NAD+ dependent dehydrogenase responsible for oxidation of 5-FDR into 5-fluoro-5-deoxy-lactone, followed by hydrolysis to 5-FHPA. The identity of 5-FHPA in the fermentation broth was confirmed by synthesis of a reference compound and then co-correlation by 19F-NMR and GC-MS analysis. The occurrence of 5-FHPA proves the existence of a new fluorometabolite pathway.

AB - (2R3S4S)-5-Fluoro-2,3,4-trihydroxypentanoic acid (5-FHPA) has been discovered as a new fluorometabolite in the soil bacterium Streptomyces sp. MA37. Exogenous addition of 5-fluoro-5-deoxy-D-ribose (5-FDR) into the cell free extract of MA37 demonstrated that 5-FDR was an intermediate to a range of unidentified fluorometabolites, distinct from fluoroacetate (FAc) and 4-fluorothreonine (4-FT). Bioinformatics analysis allowed identification of a gene cluster (fdr), encoding a pathway to the biosynthesis of 5-FHPA. Over-expression and in vitro assay of FdrC indicated that FdrC is a NAD+ dependent dehydrogenase responsible for oxidation of 5-FDR into 5-fluoro-5-deoxy-lactone, followed by hydrolysis to 5-FHPA. The identity of 5-FHPA in the fermentation broth was confirmed by synthesis of a reference compound and then co-correlation by 19F-NMR and GC-MS analysis. The occurrence of 5-FHPA proves the existence of a new fluorometabolite pathway.

U2 - 10.1039/C4SC03540B

DO - 10.1039/C4SC03540B

M3 - Article

SN - 2041-6539

VL - 6

SP - 1414

EP - 1419

JO - Chemical Science

JF - Chemical Science

IS - 2

ER -

Identification of a fluorometabolite from Streptomyces sp. MA37: (2R,3S,4S)-5-Fluoro-2,3,4-trihydroxypentanoic acid

Abstract

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