First enzyme driven biocatalytic creation of nucleic acid structure blocks

Overview

• Post By : Kumar Jeetendra


• Source: TU Graz University of Technology


• Date: 15 Dec,2020

Researchers in TU Graz and acib succeed in the first enzyme-driven biocatalytic synthesis of lipoic acid building blocks. This facilitates the development of antiviral agents and RNA-based therapeutics.

Because of this COVID 19 pandemic and the related intensive search for therapeutics and vaccines, the chemical substance class of nucleosides is undergoing an enormous increase in interest. Organic and synthetic nucleosides have an antiviral effect and can act as building blocks of ribonucleic acids (RNA). When integrated into RNA, book interactions within the macromolecule result with positive consequences for stability and biological efficacy.

In medicinal chemistry, the molecular family of carbon (C)-nucleosides is especially in demand. These vary from the naturally more frequently occurring nitrogen (N)-nucleosides – the classical building blocks of RNA – at the way the sugar is linked to the so-called nucleic base. Rather than a carbon-nitrogen bond, C-nucleosides have a carbon-carbon bond. This is biochemically a lot more stable and gives active ingredients a more biological half-life. For the first time, two researchers in Graz University of Technology and the acib competence center (Austrian Centre of Industrial Biotechnology) have now succeeded in biocatalytically producing C-nucleosides with the help of enzymes. The concrete results have been published in Nature Communications.

Bernd Nidetzky, Head of the Institute of Biotechnology and Bioprocess Engineering at TU Graz and at the same time Scientific Director of the Austrian Centre of Industrial Biotechnology (acib), and Martin Pfeiffer from acib found and characterized in a study the enzyme”YeiN”, which could link both nucleoside building blocks ribose-5-phosphates and uracil by means of a Particular carbon bond. They are the first researchers worldwide to demonstrate an enzyme that’s a suitable biocatalyst for the production of C-nucleosides.

Efficient and eco-friendly Manufacturing
With the support of the catalytic power of”YeiN”, the Graz-based firm was able to produce several derivatives of the major C-nucleoid pseudouridine. They were also able to show that one of these derivatives can be incorporated into RNA and thus enable the modification of RNA. This is particularly relevant for the creation of RNA-based therapeutic products, as the incorporation of pseudouridine into the RNA increases stability and half-life and so boosts the efficacy of therapeutic RNA, such as a vaccine.

Depending on the findings published in Nature Communications, study can now be conducted to expand the substrate spectrum of”YeiN”. The goal? The biocatalytic synthesis of additional relevant C-nucleosides.

RNA vaccines
The first comprehensive vaccinations from COVID-19 with RNA vaccines have been operating for a couple of days. These completely novel vaccines contain genetic information of the pathogen and induce cells to produce a viral protein, which is then presented to the immune system. The subsequent immune response protects the body from a genuine virus infection.

The C-nucleoside based medication Remdesivir contains these necessary antiviral properties and is effective against a number of RNA viruses, such as corona and ebola viruses. The active ingredient has received conditional approval in the EU for the treatment of COVID-19 patients. The biocatalytic production of C-nucleosides could provide further impetus for this new hope in addition to RNA vaccines according to C-nucleosides.