title: Structure-guided design and biosynthesis of a novel FR-900098 analogue as a potent Plasmodium falciparum 1-deoxy-D-xylulose-5-phosphate reductoisomerase (Dxr) inhibitor.
abstract: We report here the enzymatic biosynthesis of FR-900098 analogues and establish an in vivo platform for the biosynthesis of an N-propionyl derivative FR-900098P. FR-900098P is found to be a significantly more potent inhibitor of Plasmodium falciparum 1-deoxy-D-xylulose 5-phosphate reductoisomerase (PfDxr) than the parent compound, and thus a more promising antimalarial drug candidate.
authors.affiliation: Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 W. Gregory Drive, Urbana, IL 61801, USA.
authors.forename: Ryan E
authors.initials: RE
authors.lastname: Cobb
authors.forename: Brian
authors.initials: B
authors.lastname: Bae
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.forename: Matthew A
authors.initials: MA
authors.lastname: DeSieno
authors.forename: Satish K
authors.initials: SK
authors.lastname: Nair
authors.forename: Huimin
authors.initials: H
authors.lastname: Zhao
mesh_terms: D019747:Aldose-Ketose Isomerases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000962:Antimalarials / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D015195:Drug Design; D005578:Fosfomycin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology*
chemical_list: D000962:Antimalarials; D005578:Fosfomycin; C024639:3-(N-acetyl-N-hydroxy)aminopropylphosphonic acid; C114231:1-deoxy-D-xylulose 5-phosphate reductoisomerase; D019747:Aldose-Ketose Isomerases