Fosmidomycin

Not to be confused with Fosfomycin.

Fosmidomycin is an antibiotic that was originally isolated from culture broths of bacteria of the genus Streptomyces.^[1] It specifically inhibits DXP reductoisomerase, a key enzyme in the non-mevalonate pathway of isoprenoid biosynthesis. It is a structural analogue of 2-C-methyl-D-erythrose 4-phosphate. It inhibits the E. coli enzyme with a KI value of 38 nM (4), MTB at 80 nM, and the Francisella enzyme at 99 nM.^[2] Several mutations in the E. coli DXP reductoisomerase were found to confer resistance to fosmidomycin.^[3][4]

Fosmidomycin

Clinical data
ATC code	none
Identifiers
IUPAC name 3-[Formyl(hydroxy)amino]propylphosphonic acid
CAS Number	66508-53-0 N
PubChem CID	572
DrugBank	DB02948 Y
ChemSpider	555 Y
UNII	5829E3D9I9
ChEBI	CHEBI:443725 Y
ChEMBL	ChEMBL203125 Y
CompTox Dashboard (EPA)	DTXSID70216712
Chemical and physical data
Formula	C4H10NO5P
Molar mass	183.100 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=P(O)(O)CCCN(O)C=O
InChI InChI=1S/C4H10NO5P/c6-4-5(7)2-1-3-11(8,9)10/h4,7H,1-3H2,(H2,8,9,10) Y Key:GJXWDTUCERCKIX-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Use in malaria

The discovery of the non-mevalonate pathway in malaria parasites has indicated the use of fosmidomycin and other such inhibitors as antimalarial drugs.^[5] Indeed, fosmidomycin has been tested in combination treatment with clindamycin for treatment of malaria with favorable results.^[6][7][8] It has been shown that an increase in copy number of the target enzyme (DXP reductoisomerase) correlates with in vitro fosmidomycin resistance in the lethal malaria parasite, Plasmodium falciparum.^[9]