Project Details
Projekt
Coordination Funds
Applicant
Professorin Dr. Jennifer Andexer
Subject Area
Biological and Biomimetic Chemistry
Term
since 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 510974120
The sustainable and environmentally friendly production of building blocks for fine chemicals, pharmaceuticals, and bulk chemicals is an urgent and important task and requires a re-thinking of current established views. Biocatalytic systems using renewable and sustainable feedstocks and energy sources will be key components to achieve this goal, as enzymes operate at physiological temperatures, have favourable selectivity, substrate range, and catalytic properties, and can be produced from renewable sources. Many enzymes are dependent on an inorganic or organic cofactor, a non-protein molecule that is crucial for carrying out the biocatalytic reaction. Some of these cofactors require complex (re)generation systems. S-adenosyl-L-methionine (SAM, AdoMet) is one of the most versatile cofactors and is involved in a remarkably wide range of reaction types. SAM is used as a cosubstrate in almost all life forms. The most prominent function of SAM is to serve as a methyl group donor for methyltransferases (MTs). However, all substituents at the sulfonium ion are involved in various SAM-dependent enzymatic reactions, and different enzyme families use SAM as a source of aminopropyl- and adenosyl groups (or radicals), as amino donor, or as a source of ylides. This versatility makes SAM-dependent enzymes promising tools for biocatalysis. Over the past 10 years, interest in making this cofactor accessible for sustainable catalysis and diversify the accessible products has steadily increased. Recent advances in the fields of regeneration systems and cofactor analogues, many of which originated from members of the proposed FOR, bring sustainable application within reach. The FOR aims to gain a comprehensive understanding of the full spectrum of SAM-dependent biocatalysis, extending beyond methyl transfer and utilizing physiological and alternative substrates. A thorough understanding of SAM-dependent reactions, the underlying mechanisms, and the techniques to control them are the shared objectives of the first funding period. Establishing a biocatalytic platform including in vitro and in vivo systems for the sustainable use of SAM-dependent enzymes is the main objective of a second anticipated funding period. Using the complete range of SAM-catalyzed chemistry, such a platform will be used to make a wide variety of compounds accessible and to create orthogonal pathways. In the first funding phase, selected enzyme systems of particular novelty will be studied with respect to their catalytic mechanisms and their function in biological systems. We will investigate their ability to cooperate in multienzyme reactions, their substrate promiscuity, and their suitability as scaffolds for enzyme engineering. An exploratory analysis of SAM analogues' usefulness as components in alternative metabolic pathways and in vivo SAM regeneration systems will be conducted in addition to employing them for the characterisation of enzyme processes and product diversification.
DFG Programme
Research Units
