New enzyme-based method creates key drug building blocks from simple materials

Researchers have developed a new chemical process using proteins to build chiral oxazolidinones directly from simple alkenes. Chiral oxazolidinones are important molecular rings used widely in drug discovery and laboratory synthesis. They play a special role in creating next-generation antibiotics that fight drug-resistant strains of Mycobacterium tuberculosis. Older chemical methods often depend on starting materials called enantiopure amino alcohols. While scientists previously knew how to build chirality at certain positions, methods to shape the correct stereocentre near the oxygen atom remained poorly developed. The new study introduces a haemprotein-catalysed reaction cascade that turns basic alkenes into clinical and discovery-stage oxazolidinones. This discovery pushes forward haemprotein-driven reactions by working on unactivated alkenes, a type of chemical input previously restricted to connected systems like styrenes. Computer-based analysis shows that specific protein mutations made through directed evolution drive the selective formation of these products. The work was carried out by researchers from institutions including the California Institute of Technology and the University of Pittsburgh.