A biosynthetic pathway in bacteria includes a a carboxylase enzyme which adds CO2 to a precursor molecule, producing a highly unusual antibiotic called malonomycin.
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
