Identification of Fluorinases from Streptomyces sp MA37, Norcardia brasiliensis, and Actinoplanes sp N902‐109 by Genome Mining. Issue 3 (21st January 2014)

• Record Type: Journal Article
• Authors: Deng, Hai; Ma, Long; Bandaranayaka, Nouchali; Qin, Zhiwei; Mann, Greg; Kyeremeh, Kwaku; Yu, Yi; Shepherd, Thomas; Naismith, James H.; O'Hagan, David
• Is Part Of: Chembiochem. Volume 15:Issue 3(2014)
• Page Start: 364
• Page End: 368
• Publication Date: 2014-01-21
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201300732
• Languages: English
• ISSNs: 1439-4227

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>The fluorinase is an enzyme that catalyses the combination of <italic>S</italic>‐adenosyl‐<sc>L</sc>‐methionine (SAM) and a fluoride ion to generate 5′‐fluorodeoxy adenosine (FDA) and <sc>L</sc>‐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 <italic>Streptomyces cattleya</italic>, 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 <italic>Streptomyces</italic> sp. MA37, <italic>Nocardia brasiliensis</italic>, and an <italic>Actinoplanes</italic> sp. have high homology (80–87 % identity) to the original <italic>S. cattleya</italic> enzyme. They all possess a characteristic 21‐residue loop. The three newly identified genes were overexpressed in <italic>E. coli</italic> and shown to be fluorination enzymes. An X‐ray crystallographic study of the <italic>Streptomyces</italic> sp. MA37 enzyme demonstrated that it is almost identical in structure to the original fluorinase. Culturing of the <italic>Streptomyces</italic> sp. MA37 strain demonstrated that it not only also elaborates the fluorometabolites, fluoroacetate and 4‐fluorothreonine, similar to <italic>S. cattleya</italic>, 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.</p> </abstract>