Biocatalytic methylation and demethylation via a shuttle catalysis concept involving corrinoid proteins

• Published in: Communications chemistry 2018-11, Vol.1 (1), Article 82
• Main Authors: Farnberger, Judith E., Richter, Nina, Hiebler, Katharina, Bierbaumer, Sarah, Pickl, Mathias, Skibar, Wolfgang, Zepeck, Ferdinand, Kroutil, Wolfgang
• Format: Article
• Language: English
• Subjects: 38/23; 38/44; 631/92/603; 631/92/607/1172; 82/80; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Ethers; Methylation; Phenols; Proteins; Reagents; Regioselectivity; Substitutes
• ISSN: 2399-3669; 2399-3669
• DOI: 10.1038/s42004-018-0083-2

Synthetically established methods for methylation of phenols and demethylation of methyl phenyl ethers rely in general on hazardous reagents or/and harsh reaction conditions and are irreversible. Consequently, alternative regioselective methods for the reversible formation and breakage of C-O-ether bonds to be performed under mild and sustainable conditions are highly desired. Here we present a biocatalytic shuttle concept making use of corrinoid-dependent methyl transferases from anaerobic bacteria. The two-component enzymatic system consists of a corrinoid protein carrying the cofactor and acting as methyl group shuttle, and a methyltransferase catalyzing both methylation and demethylation in a reversible fashion. Various phenyl methyl ethers are successfully demethylated and serve in addition as sustainable methylating agents for the functionalization of various substituted catechols. Therefore, this methyl transfer approach represents a promising alternative to common chemical protocols and a valuable add-on for the toolbox of available biocatalysts. Regioselective methods for the reversible formation and breakage of C-O-ether bonds under mild conditions are desired. Here, the authors present a biocatalytic shuttle concept using corrinoid-dependent methyl transferases for demethylating various phenyl methyl ethers and functionalizing substituted catechols.