Biocatalysts are increasingly used in industrial synthetic chemistry, particularly in cases in which chemical routes are difficult to implement.  For instance, NAD(P)H-dependent oxidoreductases are valuable tools for synthesis of chiral compounds. However, the expensive cost of the cofactors requires in situ cofactor regeneration for preparative applications. To help solve this problem, we have developed an enzymatic system based on phosphite dehydrogenase (PTDH) to regenerate the reduced nicotinamide cofactors NADH and NADPH. We used directed evolution to address one of the main limitations with the wild-type PTDH enzyme, its low stability. Using random mutagenesis and high throughput screening we were able to create a mutant with a half-life of thermal inactivation at 45°C that is >7000-fold greater than that of the parent enzyme.  Another area in which biocatalysts are increasingly being used is in the production of small secondary metabolites, particularly antibiotics.  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.  We have worked to develop an E. coli strain capable of producing these antimalarial drugs.  Metabolic engineering strategies aimed at optimizing gene expression and increasing cellular substrate concentrations are also being 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.