Antibiotics containing P-C bonds (phosphonates and phoshinates) are a small but growing class of compounds with important biological activities.  Phosphonates have been shown to display a wide range of antibacterial, antiviral, pesticidal, and anti-cancer properties.  The phosphonic acid antibiotics fosmidomycin and FR-900098 represent a new class of antimalarial compounds that can be used to inhibit the nonmevalonate pathway for isoprenoid biosynthesis in the malaria-causing parasite Plasmodium falciparum.  Although no biosynthetic pathway for fosmidomycin has been elucidated as of yet, the biosynthetic pathway for FR-900098 has been recently cloned from Streptomyces rubellomurinus and heterologously expressed in Streptomyces lividans.  Here we report the creation of an E. coli strain capable of producing the antimalarial drug FR-900098.  We present here the construction of an artificial gene cluster that contains ten heterologous genes all under the control of individual T7 promoters that converts cellular phosphoenoylpyruvate (PEP) and acetyl CoA into FR-900098.  Metabolic engineering strategies aimed at optimizing gene expression and increasing cellular PEP and acetyl CoA concentrations are also explored.  In parallel to our work in E. coli, we also explore the possibility of improving the production of FR-900098 in Streptomyces lividans using metabolic engineering.