SB-203207

Sulfonamides and sulfamates are a group of organosulfur compounds that contain the signature sulfamoyl structural motif. These compounds were initially only known as synthetic antibacterial drugs but were later also discovered as natural products. Eight highly potent examples have been isolated from actinomycetes to date, illustrating the large biosynthetic repertoire of this bacterial genus. For the biosynthesis of these compounds, several distinct and unique biosynthetic machineries have been discovered, capable to generate the unique S–N bond. For the creation of novel, second generation natural products by biosynthetic engineering efforts, a detailed understanding of the underlying enzyme machinery toward potent structural motifs is crucial. In this review, we aim to summarize the current state of knowledge on sulfonamide and sulfamate biosynthesis. A detailed discussion for the secondary sulfamate ascamycin, the tertiary sulfonamide sulfadixiamycin A, and the secondary sulfonamide SB-203208 is provided and their bioactivities and mode of actions are discussed.

Natural products are an important source of medicinal seeds. The discovery of novel biosynthetic enzymes from nature is important for their use as biocatalysts for the enzymatic synthesis of useful natural products. In addition, genetics and structural biology developments have enabled the engineering of enzymes for the production of unnatural analogs of bioactive natural products. In this review, I describe the recent research on these two topics, the exploitation of a novel secondary metabolite enzyme involved in the biosynthesis of the sulfonamide natural product antibiotic SB-203208, and the production of unnatural bioactive depsipeptides by reconstruction of the modular enzyme assembly lines in the microbial host.