Project Details
Projekt
Biosynthesis and utilisation of SAM diastereomers as tools for the characterisation of SAM-dependent enzymes and product diversification
Applicant
Professorin Dr. Jennifer Andexer
Subject Area
Biological and Biomimetic Chemistry
Term
since 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 510974120
(S,S)-S-adenosylmethionine (SAM) contains six stereocentres, four of those are fixed through the ribose configuration of the adenosine moiety. Another stereocentre is defined through the alpha-carbon configuration of methionine, and the last one at the sulfonium centre is introduced by methionine adenosyltransferase (MAT) during SAM biosynthesis. Especially the sulfonium epimer is of relevance, as it is an inhibitor for methyltransferases (MTs) and develops non-enzymatically, especially in in vitro applications. The alpha-carbon epimer is similarly interesting, as it might be present in racemic mixtures of methionine analogues used for product diversification. In addition, both types of SAM diastereomers have the potential to lead to different products in reactions catalysed by SAM-dependent enzymes. This project focuses on the biocatalytic synthesis of the corresponding four SAM diastereomers using MATs, chlorinases and SAM hydrolases, and their interaction with different types of SAM-dependent enzymes, covering MTs, radical SAM enzymes, and enzymes using the SAM aminocarboxypropyl (ACP) group. After a systematic analysis of different types of SAM-dependent enzymes present in the planned FOR with the SAM diastereomers regarding acceptance, substrate binding and product outcome, the suitability of SAM diastereomers as strategy for the development of orthogonal pathways in vivo will be explored.
DFG Programme
Research Units
