Nonenzymatic generation

Pagola S, Stephens P, Bohle D, Kosar A, Madsen S. The structure of malaria pigment beta-hematin. Nature 2000 404 307-310. Schwarzer E, Kuhn H, Valente E, Arese P. Malaria-parasitized erythrocytes and hemozoin nonenzymatically generate large amounts of hydroxy fatty acids that inhibit monocyte functions. Blood 2003 101 722-728. 

In 1996, the first successful combination of an enzymatic with a nonenzymatic transformation within a domino process was reported by Waldmann and coworkers [6]. These authors described a reaction in which functionalized bicy-clo[2.2.2]octenediones were produced by a tyrosinase (from Agaricus bisporus) -catalyzed oxidation of para-substituted phenols, followed by a Diels-Alder reaction with an alkene or enol ether as dienophile. Hence, treatment of phenols such as 8-1 and an electron-rich alkene 8-4 in chloroform with tyrosinase in the presence of oxygen led to the bicyclic cycloadducts 8-5 and 8-6 in moderate to good yield (Scheme 8.1). It can be assumed that, in the first step, the phenol 8-1 is hydroxylated by tyrosinase, generating the catechol intermediate 8-2, which is then again oxidized enzy-... 

Kim, K., Rhee, S.G., and Stadtman, E.R. (1985) Nonenzymatic cleavage of proteins by reactive oxygen species generated by dithiothreitol and iron./. Biol. Chem. 260, 15394-15397. 

For the hydrolysis of phosphate esters under mild conditions, metal ions and metal complexes are the most efficient nonenzymatic reagents currently available. However, they do not reach the catalytic efficiency of enzymes, and higher reactivities are desirable in view of applications. To mimic enzymatic dinuclear sites is a strategy to generate more efficient artificial phosphoesterases. 

This product undergoes several nonenzymatic transitions, losing formaldehyde and generating a carbonium ion, +CH3, that can methylate nitrogenous bases on DNA ... 

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