Enzymatic synthesis of 3'-hydroxyacetaminophen catalyzed by tyrosinase.
3'-Hydroxyacetaminophen, a catechol metabolite of N-acetyl-p-aminophenol (acetaminophen) and N-acetyl-m-aminophenol (a structural analogue of acetaminophen and considered as a possible alternative because it is not hepatotoxic), is enzymatically synthesized for the first time using mushroom tyrosinase. Although reported to be weakly hepatotoxic in vivo, this catechol derivative of acetaminophen is not commercially available. This compound was obtained from its monophenolic precursor, acetaminophen, using the enzyme tyrosinase in the presence of an excess of ascorbic acid, thus reducing back the o-quinone product of catalytic activity to the catechol acetaminophen derivative. A mathematical model of the system is proposed, which is also applicable to the tyrosinase-mediated synthesis of any o-diphenolic compound from its corresponding monophenol. This synthesis procedure is continuous, easy to perform and control, and adaptable to a bioreactor with the immobilized enzyme for industrial purposes in a nonpolluting way.
Valero
Edelmira
E
GMB: Grupo de Modelización en Bioquímica, Departamento de Química-Física, Escuela Politécnica Superior, Universidad de Castilla-La Mancha, Campus Universitario, E-02071-Albacete, Spain. edelmira.valero@uclm.es
Lozano
M Isabel
MI
Varón
Ramón
R
García-Carmona
Francisco
F
D000082:Acetaminophen / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry*; D000363:Agaricales / Q000201:enzymology*; D001205:Ascorbic Acid / Q000737:chemistry*; D002384:Catalysis; D003198:Computer Simulation; D004800:Enzymes, Immobilized / Q000737:chemistry; D008956:Models, Chemical; D014442:Monophenol Monooxygenase / Q000737:chemistry*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
C488329:3'-hydroxyacetaminophen; D004800:Enzymes, Immobilized; D000082:Acetaminophen; D014442:Monophenol Monooxygenase; D001205:Ascorbic Acid