A vitamin K-dependent carboxylase is involved in antibiotic biosynthesis
Authors: Brian J C Law, Ying Zhuo, Michael Winn, Daniel Francis, Yingxin Zhang, Markiyan Samborskyy, Annabel Murphy, Lujing Ren, Peter F Leadlay, Jason Micklefield
Journal: Nature Catalysis
Publication Date: 26 November, 2018
Department of: Chemistry
Scientists discover a new route to antibiotics.
Scientists at the University of Manchester have discovered a new pathway in bacteria that produces an unusual antibiotic. The new pathway includes a carboxylase enzyme that adds CO2 to the structure of an antibiotic called malonomycin. The addition of the CO2 group is essential for the antimicrobial activity – precursors lacking the CO2 group exhibit no antibiotic properties.
The malonomycin carboxylase is like no other enzyme that has been characterised in bacteria so far. It is most similar to a carboxylase enzyme in human cells, which uses vitamin K to add CO2 to proteins in our bodies, triggering essential physiological responses including blood coagulation. Clinically important anticoagulant drugs, such as warfarin, work by blocking the function of the human vitamin K-dependent carboxylase.
The discovery of an antibiotic-producing carboxylase enzyme in bacteria that is similar to the human carboxylase responsible for blood clotting was a major surprise. The findings might lead to the discovery of new antibiotics and may also provide new ways of making antibiotics, which are urgently needed to combat emerging drug-resistant pathogens.
- Antibiotics are compounds found widely in natures that kill microbial pathogens (superbugs) which cause infectious diseases.
- Microbial pathogens have evolved which are resistant to the antibiotics in current use.
- New pathways to antibiotics with unusual structures can potentially provide new drugs to treat infectious diseases.