title: Role of substituents on the reactivity and product selectivity in reactions of naphthalene derivatives catalyzed by the orphan thermostable cytochrome P450, CYP175A1.
abstract: The thermostable nature of CYP175A1 enzyme is of potential interest for the biocatalysis at ambient temperature or at elevated temperature under environmentally benign conditions. Although little is known about the substrate selectivity of this enzyme, the biocatalytic activities of CYP175A1 on different substituted naphthalenes have been studied in oxidative pathway, and the effect of the substituent on the reaction has been determined. The enzyme first acts as a peroxygenase to convert these substituted naphthalenes to the corresponding naphthols, which subsequently undergo in-situ oxidative dimerization to form dyes of different colors possibly by the peroxidase-type activity of CYP175A1. The product analyses and kinetic measurements suggested that the presence of electron releasing substituent (ERS) in the substrate enhanced the substrate conversion, whereas the presence of electron withdrawing substituent (EWS) in the substrate drastically reduced the substrate conversion. The position of the ERS in the substrate was also found to play an important role in the transformation of the substrate. The results further demonstrate that mutation of the Leu80 residue to Phe enhances the reactivity of the enzyme by favoring the substrate association in the active site. The observed rates of the enzymatic oxygenation reaction of the substituted naphthalenes followed the Hammett correlation of substituent effect, supporting aromatic electrophilic substitution mechanism catalyzed by the cytochrome P450 enzyme.
authors: Department of Chemical Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400005, India.
authors: Shibdas
authors: S
authors: Banerjee
authors: Department of Chemical Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400005, India.
authors: Sandeep
authors: S
authors: Goyal
authors: Department of Chemical Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400005, India. Electronic address: shyamal@tifr.res.in.
authors: Shyamalava
authors: S
authors: Mazumdar
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D057075:Enzyme Assays; D009281:Naphthalenes / Q000737:chemistry* / Q000378:metabolism; D013053:Spectrophotometry
chemical_list: D001426:Bacterial Proteins; D009281:Naphthalenes; D003577:Cytochrome P-450 Enzyme System
keywords: CYP175A1; Cytochrome P450; Hydroxylation; Oxidative dimerization; Substituted naphthalene