Diketopiperazines, DKPs, make up a large group of natural products with diverse structures and biological activities. Bicyclomycin is a broad-spectrum DKP antibiotic with unique structure and function.
Researchers in the Li Group have identified a new biosynthetic pathway for antibiotic bicyclomycin. This pathway employs a tRNA-dependent cyclcodipeptide synthase to synthesize the DKP core, and six iron-dependent oxidases to functionalize the core.
Genome mining revealed that this pathway is widely distributed in an opportunistic human pathogen Pseudomonas aeruginosa. The work, published in Biochemistry, as part of the Future of Chemistry special issue and highlighted in a Viewpoint article in Biochemistry “Biosynthesis of the Antibiotic Bicyclomycin in Soil and Pathogenic Bacteria,” sheds light on the intriguing oxidation chemistry that converts a simple DKP into a powerful antibiotic.
The Li Group's work also characterized two out of six oxygenases that catalyze regio- and stereo-specific hydroxylation reactions of difficult-to-modify carbon centers and add these enzymes to a growing list of biocatalysts that may have industrial utility.