Unchecked antibiotic resistance could result in an estimated 10 million deaths every year by 2050, while guesses on cost to the global economy go as high as $70 trillion in lost productivity.
The researchers found that CO2 was introduced into the malonomycin structure, by a carboxylase enzyme that has never been characterized in bacteria before. Malonomycin carboxylase 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.
Jason Micklefield, Professor of Chemical Biology at the Manchester Institute of Biotechnology, who led the study, said, "using a combination of bioinformatics, gene editing and in vitro experiments, we have discovered a highly unusual biosynthetic pathway to the antibiotic malonomycin. This could pave the way for a new kind of antibiotic production process.”
Citation: Brian J. C. Law, Ying Zhuo, Michael Winn, Daniel Francis, Yingxin Zhang, Markiyan Samborskyy, Annabel Murphy, Lujing Ren, Peter F. Leadlay&Jason Micklefield, 'A vitamin K-dependent carboxylase orthologue is involved in antibiotic biosynthesis', Nature Catalysis, DOI 10.1038/s41929-018-0178-2