Work

Tryptophan 7-Halogenase (PrnA) Structure Suggests a Mechanism for Regioselective Chlorination

Year: 2005

Type: article

Abstract: Chlorinated natural products include vancomycin and cryptophycin A. Their biosynthesis involves regioselective chlorination by flavin-dependent halogenases. We report the structural characterization of tryptophan 7-halogenase (PrnA), which regioselectively chlorinates tryptophan. Tryptophan and flavin adenine dinucleotide (FAD) are separated by a 10 angstrom-long tunnel and bound by distinct enzyme modules. The FAD module is conserved in halogenases and is related to flavin-dependent monooxygenases. On the basis of biochemical studies, crystal structures, and by analogy with monooxygenases, we predict that FADH2 reacts with O2 to make peroxyflavin, which is decomposed by Cl-. The resulting HOCl is guided through the tunnel to tryptophan, where it is activated to participate in electrophilic aromatic substitution.

Source: Science

DOI: 10.1126/science.1116510

Authors: Changjiang Dong, Silvana Flecks, Susanne Unversucht, Caroline Haupt, Karl-Heinz van Pée, James H. Naismith

Institutions: University of St Andrews, Technische Universität Dresden

Language: English

Topic: Microbial Natural Products and Biosynthesis

Subfield: Applied Microbiology and Biotechnology

Field: Immunology and Microbiology

Domain: Life Sciences

Open Access status: green

Funders: Wellcome Trust, Biotechnology and Biological Sciences Research Council

Awards: G6654353843, G952359054