Halogenation of unactivated carbon centers in natural product biosynthesis: trichlorination of leucine during barbamide biosynthesis.
The in vitro reconstitution of leucine halogenation during barbamide biosynthesis has been accomplished. It has been demonstrated that the triple chlorination of the unactivated pro-R methyl group of the peptidyl carrier protein-tethered l-Leu substrate is carried out by the tandem action of two nonheme iron(II)-dependent halogenases, BarB1 and BarB2. Investigation of the substrate specificities of each of the halogenating enzymes revealed their complementary roles in the generation of trichloroleucine.
Galonić
Danica P
DP
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Vaillancourt
Frédéric H
FH
Walsh
Christopher T
CT
D000458:Cyanobacteria / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D006843:Hydrocarbons, Chlorinated / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism*; D013844:Thiazoles / Q000378:metabolism*
D006843:Hydrocarbons, Chlorinated; D013844:Thiazoles; C100545:barbamide; D007930:Leucine