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Issue 43, 2013
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Chemoenzymatic synthesis and in situ application of S-adenosyl-l-methionine analogs

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Abstract

Analogs of S-adenosyl-L-methionine (SAM) are increasingly applied to the methyltransferase (MT) catalysed modification of biomolecules including proteins, nucleic acids, and small molecules. However, SAM and its analogs suffer from an inherent instability, and their chemical synthesis is challenged by low yields and difficulties in stereoisomer isolation and inhibition. Here we report the chemoenzymatic synthesis of a series of SAM analogs using wild-type (wt) and point mutants of two recently identified halogenases, SalL and FDAS. Molecular modelling studies are used to guide the rational design of mutants, and the enzymatic conversion of L-Met and other analogs into SAM analogs is demonstrated. We also apply this in situ enzymatic synthesis to the modification of a small peptide substrate by protein arginine methyltransferase 1 (PRMT1). This technique offers an attractive alternative to chemical synthesis and can be applied in situ to overcome stability and activity issues.

Graphical abstract: Chemoenzymatic synthesis and in situ application of S-adenosyl-l-methionine analogs

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Publication details

The article was received on 20 Aug 2013, accepted on 19 Sep 2013 and first published on 19 Sep 2013


Article type: Paper
DOI: 10.1039/C3OB41702F
Org. Biomol. Chem., 2013,11, 7606-7610

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    Chemoenzymatic synthesis and in situ application of S-adenosyl-L-methionine analogs

    M. Thomsen, S. B. Vogensen, J. Buchardt, M. D. Burkart and R. P. Clausen, Org. Biomol. Chem., 2013, 11, 7606
    DOI: 10.1039/C3OB41702F

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