Carbon-carbon bonds in fatty acids are generated by condensation of acyl-thioesters and malonyl-thioesters, carried by either CoA or an acyl carrier protein (ACP). In E. coli and related bacteria the first fatty acid carbon-carbon bond formed is between acetyl-CoA and malonyl-S-ACP by FabH, which is likely rate limiting in vivo, Figure . Inhibition of FabH with thio lactomycin in vivo leads to overall growth inhibition, revealing FabH and homologs are valid drug targets. Thus, a better understanding of FabH catalysis will inform drug discovery efforts.