Fosmidomycin is an

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...

that was originally isolated from culture broths of bacteria of the genus ''

Streptomyces ''Streptomyces'' is the largest genus of Actinomycetota and the type genus of the family Streptomycetaceae. Over 500 species of ''Streptomyces'' bacteria have been described. As with the other Actinomycetota, streptomycetes are gram-positive, ...

''. It specifically inhibits DXP reductoisomerase, a key enzyme in the

non-mevalonate pathway The non-mevalonate pathway—also appearing as the mevalonate-independent pathway and the 2-''C''-methyl-D-erythritol 4-phosphate/1-deoxy-D-xylulose 5-phosphate (MEP/DOXP) pathway—is an alternative metabolic pathway for the biosynthesis of the is ...

isoprenoid The terpenoids, also known as isoprenoids, are a class of naturally occurring organic chemicals derived from the 5-carbon compound isoprene and its derivatives called terpenes, diterpenes, etc. While sometimes used interchangeably with "terpenes", ...

biosynthesis. It is a structural analogue of

2-C-methyl-D-erythrose 4-phosphate 2-''C''-Methyl--erythritol 4-phosphate (MEP) is an intermediate on the MEP pathway (non-mevalonate pathway) of isoprenoid precursor biosynthesis. It is the first committed metabolite on that pathway on the route to IPP and DMAPP. See also * DX ...

. It inhibits the ''

E. coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...

'' enzyme with a KI value of 38 nM (4), MTB at 80 nM, and the '' Francisella'' enzyme at 99 nM. Several mutations in the E. coli DXP reductoisomerase were found to confer resistance to fosmidomycin.

Use in malaria

The discovery of the

in malaria parasites has indicated the use of fosmidomycin and other such inhibitors as antimalarial drugs. Indeed, fosmidomycin has been tested in combination treatment with

clindamycin Clindamycin is an antibiotic medication used for the treatment of a number of bacterial infections, including osteomyelitis (bone) or joint infections, pelvic inflammatory disease, strep throat, pneumonia, acute otitis media (middle ear infec ...

for treatment of malaria with favorable results. 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 ''Plasmodium falciparum'' is a Unicellular organism, unicellular protozoan parasite of humans, and the deadliest species of ''Plasmodium'' that causes malaria in humans. The parasite is transmitted through the bite of a female ''Anopheles'' mosqu ...

''.

References

Antibiotics Oxidoreductase inhibitors Phosphonic acids {{antibiotic-stub