Identification of a fluorometabolite from Streptomyces sp. MA37 : (2R3S4S)-5-fluoro-2,3,4-trihydroxypentanoic acid
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(2R3S4S)-5-Fluoro-2,3,4-trihydroxypentanoic acid (5-FHPA) has been discovered as a new fluorometabolite in the soil bacterium Streptomyces sp. MA37. Exogenous addition of 5-fluoro-5-deoxy-D-ribose (5-FDR) into the cell free extract of MA37 demonstrated that 5-FDR was an intermediate to a range of unidentified fluorometabolites, distinct from fluoroacetate (FAc) and 4-fluorothreonine (4-FT). Bioinformatics analysis allowed identification of a gene cluster (fdr), encoding a pathway to the biosynthesis of 5-FHPA. Over-expression and in vitro assay of FdrC indicated that FdrC is a NAD+ dependent dehydrogenase responsible for oxidation of 5-FDR into 5-fluoro-5-deoxy-lactone, followed by hydrolysis to 5-FHPA. The identity of 5-FHPA in the fermentation broth was confirmed by synthesis of a reference compound and then co-correlation by 19F-NMR and GC-MS analysis. The occurrence of 5-FHPA proves the existence of a new fluorometabolite pathway.
Ma , L , Bartholome , A J G , Tong , M H , Qin , Z , Yu , Y , Shepherd , T , Kyeremeh , K , Deng , H & O'Hagan , D 2015 , ' Identification of a fluorometabolite from Streptomyces sp. MA37 : (2R3S4S)-5-fluoro-2,3,4-trihydroxypentanoic acid ' Chemical Science , vol 6 , no. 2 , pp. 1414-1419 . DOI: 10.1039/C4SC03540B
Copyright 2015, The Authors. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence (http://creativecommons.org/licenses/by/3.0/)
DOH thanks EPSRC and the ERC for financial support. He also acknowledges the Royal Society for a Wolfson Merit Award. KK and HD thank the Leverhulme Trust; Royal Society Africa Award (AA090088). Date of Acceptance: 26/11/2014