Polyphosphate kinases of the family 2 (PPK2) have become a popular option for the regeneration of adenosine-5’-triphosphate (ATP) in various applications. Inorganic polyphosphate (polyP) is an abundant, inexpensive and stable phosphate donor; and PPK2s can be used for the phosphorylation of AMP as well as ADP.[1]

PPK2 enzymes can be combined with other enzymes to build regeneration cycles for complex ATP-derived cofactors such as coenzyme A. Through the combination with adenosine kinase, PPK2s can also be used for the regeneration of ATP from adenosine; this is for example necessary for the regeneration of cofactors such as S adenosylmethionine (SAM) used in biocatalytic alkylation reactions.[2]

SAM-dependent methyltransferases (MTs) are found in the biosynthetic pathways of a wide range of natural products. They catalyse the regio-, stereo-, and chemoselective methylation of compounds ranging from small molecules to peptides, nucleic acids, and proteins. Due to their selectivity on the one hand, and their flexibility towards substrate and co-substrate on the other hand, they are emerging biocatalysts for application in chemical synthesis.[3]

In order to add to product diversity, the use of co-substrate analogues allows the transfer of alternative groups from SAM analogues. For this, we use linear multienzyme cascades employing methionine adenosyltransferases and introduced an extended biocatalytic cascade to synthesise the required methionine analogues from homocysteine and off-the-shelf thiols.[4]

Through this and other work, SAM-dependent MT are becoming a genuine option for in vitro and in vivo application – as biocatalysts for chemical syntheses as well as for the design and implementation of altered biosynthetic pathways using tailored MTs.