Identification of Fluorinases from Streptomyces sp MA37, Norcardia brasiliensis, and Actinoplanes sp N902-109 by Genome Mining

Hai Deng (Corresponding Author), Long Ma, Nouchali Bandaranayaka, Zhiwei Qin, Greg Mann, Kwaku Kyeremeh, Yi Yu, Thomas Shepherd, James Naismith, David O'Hagan (Corresponding Author)

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

The fluorinase is an enzyme that catalyses the combination of
S-adenosyl-l-methionine (SAM) and a fluoride ion to generate
5’-fluorodeoxy adenosine (FDA) and l-methionine through
a nucleophilic substitution reaction with a fluoride ion as the
nucleophile. It is the only native fluorination enzyme that has
been characterised. The fluorinase was isolated in 2002 from
Streptomyces cattleya, and, to date, this has been the only
source of the fluorinase enzyme. Herein, we report three new
fluorinase isolates that have been identified by genome
mining. The novel fluorinases from Streptomyces sp. MA37, Nocardia
brasiliensis, and an Actinoplanes sp. have high homology
(80–87% identity) to the original S. cattleya enzyme. They all
possess a characteristic 21-residue loop. The three newly identified
genes were overexpressed in E. coli and shown to be
fluorination enzymes. An X-ray crystallographic study of the
Streptomyces sp. MA37 enzyme demonstrated that it is almost
identical in structure to the original fluorinase. Culturing of the
Streptomyces sp. MA37 strain demonstrated that it not only
also elaborates the fluorometabolites, fluoroacetate and 4-fluorothreonine,
similar to S. cattleya, but this strain also produces
a range of unidentified fluorometabolites. These are the first
new fluorinases to be reported since the first isolate, over
a decade ago, and their identification extends the range of
fluorination genes available for fluorination biotechnology.
Original languageEnglish
Pages (from-to)364-368
Number of pages5
JournalChemBioChem
Volume15
Issue number3
Early online date21 Jan 2014
DOIs
Publication statusPublished - 10 Feb 2014

Fingerprint

Streptomyces
Genes
Genome
Enzymes
Fluorination
Halogenation
Fluorides
Methionine
Fluoroacetates
Ions
Biotechnology
Adenosine
Escherichia coli
fluorinase
Substitution reactions
X-Rays
X rays

Keywords

  • biotransformations
  • enzyme catalysis
  • fluorinases
  • genome mining
  • streptomyces sp. MA

Cite this

Identification of Fluorinases from Streptomyces sp MA37, Norcardia brasiliensis, and Actinoplanes sp N902-109 by Genome Mining. / Deng, Hai (Corresponding Author); Ma, Long; Bandaranayaka, Nouchali; Qin, Zhiwei; Mann, Greg; Kyeremeh, Kwaku; Yu, Yi; Shepherd, Thomas; Naismith, James; O'Hagan, David (Corresponding Author).

In: ChemBioChem, Vol. 15, No. 3, 10.02.2014, p. 364-368.

Research output: Contribution to journalArticle

Deng, H, Ma, L, Bandaranayaka, N, Qin, Z, Mann, G, Kyeremeh, K, Yu, Y, Shepherd, T, Naismith, J & O'Hagan, D 2014, 'Identification of Fluorinases from Streptomyces sp MA37, Norcardia brasiliensis, and Actinoplanes sp N902-109 by Genome Mining', ChemBioChem, vol. 15, no. 3, pp. 364-368. https://doi.org/10.1002/cbic.201300732
Deng, Hai ; Ma, Long ; Bandaranayaka, Nouchali ; Qin, Zhiwei ; Mann, Greg ; Kyeremeh, Kwaku ; Yu, Yi ; Shepherd, Thomas ; Naismith, James ; O'Hagan, David. / Identification of Fluorinases from Streptomyces sp MA37, Norcardia brasiliensis, and Actinoplanes sp N902-109 by Genome Mining. In: ChemBioChem. 2014 ; Vol. 15, No. 3. pp. 364-368.
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AU - Deng, Hai

AU - Ma, Long

AU - Bandaranayaka, Nouchali

AU - Qin, Zhiwei

AU - Mann, Greg

AU - Kyeremeh, Kwaku

AU - Yu, Yi

AU - Shepherd, Thomas

AU - Naismith, James

AU - O'Hagan, David

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PY - 2014/2/10

Y1 - 2014/2/10

N2 - The fluorinase is an enzyme that catalyses the combination ofS-adenosyl-l-methionine (SAM) and a fluoride ion to generate5’-fluorodeoxy adenosine (FDA) and l-methionine througha nucleophilic substitution reaction with a fluoride ion as thenucleophile. It is the only native fluorination enzyme that hasbeen characterised. The fluorinase was isolated in 2002 fromStreptomyces cattleya, and, to date, this has been the onlysource of the fluorinase enzyme. Herein, we report three newfluorinase isolates that have been identified by genomemining. The novel fluorinases from Streptomyces sp. MA37, Nocardiabrasiliensis, and an Actinoplanes sp. have high homology(80–87% identity) to the original S. cattleya enzyme. They allpossess a characteristic 21-residue loop. The three newly identifiedgenes were overexpressed in E. coli and shown to befluorination enzymes. An X-ray crystallographic study of theStreptomyces sp. MA37 enzyme demonstrated that it is almostidentical in structure to the original fluorinase. Culturing of theStreptomyces sp. MA37 strain demonstrated that it not onlyalso elaborates the fluorometabolites, fluoroacetate and 4-fluorothreonine,similar to S. cattleya, but this strain also producesa range of unidentified fluorometabolites. These are the firstnew fluorinases to be reported since the first isolate, overa decade ago, and their identification extends the range offluorination genes available for fluorination biotechnology.

AB - The fluorinase is an enzyme that catalyses the combination ofS-adenosyl-l-methionine (SAM) and a fluoride ion to generate5’-fluorodeoxy adenosine (FDA) and l-methionine througha nucleophilic substitution reaction with a fluoride ion as thenucleophile. It is the only native fluorination enzyme that hasbeen characterised. The fluorinase was isolated in 2002 fromStreptomyces cattleya, and, to date, this has been the onlysource of the fluorinase enzyme. Herein, we report three newfluorinase isolates that have been identified by genomemining. The novel fluorinases from Streptomyces sp. MA37, Nocardiabrasiliensis, and an Actinoplanes sp. have high homology(80–87% identity) to the original S. cattleya enzyme. They allpossess a characteristic 21-residue loop. The three newly identifiedgenes were overexpressed in E. coli and shown to befluorination enzymes. An X-ray crystallographic study of theStreptomyces sp. MA37 enzyme demonstrated that it is almostidentical in structure to the original fluorinase. Culturing of theStreptomyces sp. MA37 strain demonstrated that it not onlyalso elaborates the fluorometabolites, fluoroacetate and 4-fluorothreonine,similar to S. cattleya, but this strain also producesa range of unidentified fluorometabolites. These are the firstnew fluorinases to be reported since the first isolate, overa decade ago, and their identification extends the range offluorination genes available for fluorination biotechnology.

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KW - enzyme catalysis

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