Numerous reports of multi-drug resistant bacterial strains have appeared in recent years, with several strains posing the threat of becoming immune against all commercially available antibiotics. It is evident that in order to prevent potential epidemic outbreaks of infectious diseases, a renewed focus on antibiotic research is highly desired, including the search for new drugs with alternative cellular targets, the investigation of the mechanisms of cytotoxicity and resistance, and the understanding of biosynthetic pathways. The threat of bioterrorism and the continuing large death toll due to infectious diseases in developing countries further underscores the need for new lines of research to combat pathogenic bacteria. Unfortunately, at this time of critical need for new antimicrobial agents, the large pharmaceutical companies have almost entirely withdrawn from this area due to small projected profits. The van der Donk group focuses on the mode of action and mechanism of biosynthesis of two classes of antibiotics that have been underexplored but have great potential for human therapeutic use, lantibiotics and phosphonate antibiotics (J. Org. Chem. 2006 71, 9561-9571.).

Relatively unexplored with respect to biosynthetic pathways are phosphonate antibiotics, despite their potential use in antibacterial, antiviral, and antiparasitic therapies. Moreover, they are used extensively in agriculture as herbicides and pesticides. A selection of these compounds is shown below. Phosphonates and phosphinates are effective antibacterial and antifungal agents because the P-C bond is resistant to hydrolysis.They exert their biological action as mimics of either carboxylic acids (eg phosphinothricin) or phosphate esters (eg FR900098). Amongst the compounds in this class, FR900098 and fosmidomycin are highly effective anti-malarial agents, fosfomycin is used clinically under the name Monurol® and is an FDA approved drug for the treatment of acute cystitis, and phosphinothricin (PT) is an intermediate in the biogenesis of bialaphos, which is commercially used as a herbicide under the names BASTA® and Liberty®. Various formulations of phosphinothricin are widely used in agriculture, with annual sales in excess of $200 million per year. Amongst natural P-C bond-containing compounds phosphinothricin is highly unusual in that it contains a C-P-C moiety.