Offering potential for development of anti-diabetic drugs having fewer side effects
A research team led by Professor Deok-kun Oh of the Department of Integrative Bioscience and Biotechnology, KU Institute of Technology, has identified the possibility of development of anti-diabetic drugs through biotransformation of polyunsaturated fatty acids to bioactive hepoxilins and trioxilins by microbial enzymes.
On January 9, 2018, the research, named “Biotransformation of polyunsaturated fatty acids to bioactive hepoxilins and trioxilins by microbial enzymes” funded by the Mid-Career Researcher Program, through the National Research Foundation grant funded by the Ministry of Science, ICT and Future Planning, Republic of Korea, was published in Nature Communications, a peer-reviewed open access scientific journal published by the Nature Publishing Group since 2010.
Diabetes mellitus (DM), commonly referred to as diabetes, is a group of metabolic disorders in which there are high blood sugar levels over a prolonged period. Recently it is reported that three out of ten adults aged over 30 suffer from or are at high risk for development of diabetes, arousing concerns and anti-diabetic drugs being widely administered can cause side effects including heart failure and weight gain. Therefore, new medicine for diabetes with fewer side effects have been urgently needed.
The research team focused on finding natural substances which can be used for treatment of diabetes. Hepoxilins (HXs) and trioxilins (TrXs) which are involved in physiological processes such as inflammation, insulin secretion and pain perception in human are metabolites of polyunsaturated fatty acids (PUFAs), including arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid, formed by 12-lipoxygenase (LOX) and epoxide hydrolase (EH) expressed by mammalian cells. They identified ten types of HXs and TrXs, produced by the prokaryote Myxococcus xanthus, of which six types are new, namely, HXB5, HXD3, HXE3, TrXB5, TrXD3 and TrXE3 and succeed in the biotransformation of PUFAs into eight types of HXs (>35% conversion) and TrXs (>10% conversion) by expressing M. xanthus 12-LOX or 11-LOX with or without EH in Escherichia coli. In conclusion, the team determined 11-hydroxy-eicosatetraenoic acid, HXB3, HXB4, HXD3, TrXB3 and TrXD3 as potential peroxisome proliferator-activated receptor-γ partial agonists.
“We developed and produced a great number of lipid mediators which don’t exist much in the human body using microbial enzymes. We expect that diverse types of lipid mediators which can be used for treatments of diabetes, inflammation and infection will be biosynthesized,” said Professor Oh.