Antibiotic Bicyclomycin

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.