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)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

91 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

Bibliographical note

Highlighted in C&E News, 2014, 92(5), p25-26

Keywords

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

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