Chemistry & Biochemistry Colloquium – Joseph Roman – Moran Research Group – The methyl transfer reaction: Nature’s convoluted solutions to a simple problem

Methylation is a ubiquitous process in all branches of life. Whether it is to regulate the expression of certain genes, or to give stability to the tertiary structure of large biomolecules, all organisms, from the tiniest microbe to the giants of the sea, use methylation to influence their life cycles. The methyltransfer reaction itself is not terribly complex, with a plethora of organisms using classic S-adenosyl methionine (SAM) dependant enzymes that do their chemistry similar to that of the Williamson ether synthesis. There are, however, examples of more complicated systems that achieve the same overall chemistry. The focus of this seminar will be on three such examples of fairly complicated enzymes. The first will be a look at a member of the Radical SAM super family that utilizes a reductive cleavage step and a new use for a highly conserved active site cystine. The second will be the flavin dependant Thymidylate Synthase, that has now been proposed to utilize two flavin bridged species as well as a polarized deprotanation step. The last enzyme will be the Acetyl-CoA/Carbon dioxide dehydrogenase multi enzyme system, which was the subject of some controversy from 1995-2006. It utilizes a unique and rather unstable cofactor along with three other enzymes to accomplish an acetylation reaction. This along with the previous two enzyme examples leaves one wondering, with such simple mechanisms available to organisms, why put stock into such complex machinery?