Engineering fluorometabolite production: fluorinase expression in Salinispora tropica Yields Fluorosalinosporamide.
Organofluorine compounds play an important role in medicinal chemistry, where they are responsible for up to 15% of the pharmaceutical products on the market. While natural products are valuable sources of new chemical entities, natural fluorinated molecules are extremely rare and the pharmaceutical industry has not benefited from a microbial source of this class of compounds. Streptomyces cattleya is an unusual bacterium in that it elaborates fluoroacetate and the amino acid 4-fluorothreonine. The discovery in 2002 of the fluorination enzyme FlA responsible for C-F bond formation in S. cattleya, and its subsequent characterization, opened up for the first time the prospect of genetically engineering fluorometabolite production from fluoride ion in host organisms. As a proof of principle, we report here the induced production of fluorosalinosporamide by replacing the chlorinase gene salL from Salinispora tropica with the fluorinase gene flA.
Eustáquio
Alessandra S
AS
Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, California 92093-0204, USA.
O'Hagan
David
D
Moore
Bradley S
BS
D039903:Actinobacteria / Q000201:enzymology* / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D005818:Genetic Engineering; D006845:Hydrocarbons, Fluorinated / Q000032:analysis* / Q000737:chemistry; D007783:Lactones / Q000032:analysis* / Q000737:chemistry; D015394:Molecular Structure; D030781:Organisms, Genetically Modified / Q000378:metabolism*; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D013302:Streptomyces / Q000378:metabolism*
D001426:Bacterial Proteins; D006845:Hydrocarbons, Fluorinated; D007783:Lactones; C529938:fluorosalinosporamide; D010088:Oxidoreductases; C495766:fluorinase