DNA is the most fundamental building block of life on earth. All genetic information organisms need to function, grow, and reproduce are stored inside of their DNA. Biochemists from the University of Münster have developed a new strategy to control the biological functions of DNA using light. The breakthrough allows researchers to improve their understanding and control of different processes that occur within a cell.
The team was headed by Professor Andrea Rentmeister of the Institute of Biochemistry at the University of Münster. The team used something known as an enzymatic cascade reaction to understand and track the functions of DNA. By sequencing successive reaction steps using different enzymes, the team could transfer so-called “photocaging” groups, which are groups that can be removed by irradiating them with light.
The work allows the researchers to transfer large residues or modifications, including the photocaging groups. The team leveraged protein engineering to engineer one enzyme in the cascade, making it possible to switch DNA functions on and off using light. Leveraging protein design allowed the team to expand the substrate spectrum of enzymes. The enzyme, in this case, is called methionine adenosyltransferases (MATs). The team examined two MATs, and modifications carried out represent a starting point for developing others with an expanded substrate spectrum.
Rentmeister says the combination of MATs with other enzymes has the potential for future cellular applications. The scientists also noted the research was an important step in implementing in-situ generated, non-natural substances for other enzymes used in epigenetic studies. Past studies were able to show that small residues, which are slight modifications to things like methyl groups, can be transferred very selectively to DNA, RNA, or proteins. The new research is a significant expansion of that past research.