Inversion of enantioselectivity of a mononuclear non-heme iron(II)-dependent hydroxylase by tuning the interplay of metal-center geometry and protein structure.

The ol' switcheroo: The enantioselectivity of an O2-dependent hydroxylation at a mononuclear non-heme iron center was switched from S to R by changing the geometry of the substrate ligand at the metal center through protein redesign. This rational approach resulted in a greater than 9000-fold enhancement in (R)-selectivity and yielded a highly active (R)-mandelate synthase. Copyright ?? 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[1]  L. Que,et al.  Iron Coordination Chemistry of Phenylpyruvate: An Unexpected kappa3-bridging mode that leads to oxidative cleavage of the C2-C3 bond. , 2005, Inorganic chemistry.

[2]  June M. Brownlee,et al.  Evidence for the mechanism of hydroxylation by 4-hydroxyphenylpyruvate dioxygenase and hydroxymandelate synthase from intermediate partitioning in active site variants. , 2011, Biochemistry.

[3]  Manfred T Reetz,et al.  Regio- and stereoselectivity of P450-catalysed hydroxylation of steroids controlled by laboratory evolution , 2011, Nature Chemistry.

[4]  K. Sanderson.  Chemistry: It's not easy being green , 2011, Nature.

[5]  Vlada B Urlacher,et al.  Cytochrome P450 monooxygenases: an update on perspectives for synthetic application. , 2012, Trends in biotechnology.

[6]  G. Challis,et al.  Engineering p-hydroxyphenylpyruvate dioxygenase to a p-hydroxymandelate synthase and evidence for the proposed benzene oxide intermediate in homogentisate formation. , 2004, Biochemistry.

[7]  Gheorghe-Doru Roiban,et al.  Achieving Regio‐ and Enantioselectivity of P450‐Catalyzed Oxidative CH Activation of Small Functionalized Molecules by Structure‐Guided Directed Evolution , 2012, Chembiochem : a European journal of chemical biology.

[8]  Son Quang Pham,et al.  Evolving P450pyr hydroxylase for highly enantioselective hydroxylation at non-activated carbon atom. , 2012, Chemical communications.

[9]  Panqing He,et al.  Two roads diverged: the structure of hydroxymandelate synthase from Amycolatopsis orientalis in complex with 4-hydroxymandelate. , 2008, Biochemistry.

[10]  E. Solomon,et al.  Spectroscopic and electronic structure studies of aromatic electrophilic attack and hydrogen-atom abstraction by non-heme iron enzymes , 2006, Proceedings of the National Academy of Sciences.

[11]  and P H Williams,et al.  Biosynthesis of the Vancomycin Group of Antibiotics: Involvement of an Unusual Dioxygenase in the Pathway to (S)-4-Hydroxyphenylglycine , 2000 .

[12]  Huimin Zhao,et al.  Inverting the enantioselectivity of P450pyr monooxygenase by directed evolution. , 2010, Chemical communications.

[13]  C. Walsh,et al.  Biosynthesis of L-p-hydroxyphenylglycine, a non-proteinogenic amino acid constituent of peptide antibiotics. , 2000, Chemistry & biology.

[14]  E. Kovaleva,et al.  Versatility of biological non-heme Fe(II) centers in oxygen activation reactions. , 2008, Nature chemical biology.

[15]  June M. Brownlee,et al.  Product analysis and inhibition studies of a causative Asn to Ser variant of 4-hydroxyphenylpyruvate dioxygenase suggest a simple route to the treatment of Hawkinsinuria. , 2010, Biochemistry.