TY - JOUR
T1 - Identification of fluorinases from streptomyces sp MA37, norcardia brasiliensis, and actinoplanes sp N902-109 by genome mining
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 H.
AU - O'Hagan, David
PY - 2014/2/10
Y1 - 2014/2/10
N2 - 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. Get on the fluor! The fluorinase enzyme from Streptomyces cattleya was identified in 2002 as the only fluorination enzyme known in biochemistry. Three additional fluorinases expressed through bacterial genome mining are now reported. These new fluorinases extend the range of genes available for developing fluorination biotechnology.
AB - 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. Get on the fluor! The fluorinase enzyme from Streptomyces cattleya was identified in 2002 as the only fluorination enzyme known in biochemistry. Three additional fluorinases expressed through bacterial genome mining are now reported. These new fluorinases extend the range of genes available for developing fluorination biotechnology.
KW - Streptomyces sp. MA
KW - biotransformations
KW - enzyme catalysis
KW - fluorinases
KW - genome mining
UR - http://www.scopus.com/inward/record.url?scp=84895075028&partnerID=8YFLogxK
U2 - 10.1002/cbic.201300732
DO - 10.1002/cbic.201300732
M3 - Article
C2 - 24449539
AN - SCOPUS:84895075028
SN - 1439-4227
VL - 15
SP - 364
EP - 368
JO - ChemBioChem
JF - ChemBioChem
IS - 3
ER -