Publication

Article Metrics

Citations


Online attention

Structure and biocatalytic scope of thermophilic flavin-dependent halogenase and flavin reductase enzymes

DOI: 10.1039/C6OB01861K DOI Help

Authors: Binuraj R. K. Menon (University of Manchester) , Jonathan Latham (University of Manchester) , Mark S. Dunstan (University of Manchester) , Eileen Brandenburger (University of Manchester) , Ulrike Klemstein (University of Manchester) , David Leys (University of Manchester) , Chinnan Karthikeyan (University of Manchester) , Michael F. Greaney (University of Manchester) , Sarah A. Shepherd (University of Manchester) , Jason Micklefield (University of Manchester)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Org. Biomol. Chem. , VOL 14 , PAGES 9354 - 9361

State: Published (Approved)
Published: September 2016
Diamond Proposal Number(s): 8997

Open Access Open Access

Abstract: Flavin-dependent halogenase (Fl-Hal) enzymes have been shown to halogenate a range of synthetic as well as natural aromatic compounds. The exquisite regioselectively of Fl-Hal enzymes can provide halogenated building blocks which are inaccessible using standard halogenation chemistries. Consequently, Fl-Hal are potentially useful biocatalysts for the chemoenzymatic synthesis of pharmaceuticals and other valuable products, which are derived from haloaromatic precursors. However, the application of Fl-Hal enzymes, in vitro, has been hampered by their poor catalytic activity and lack of stability. To overcome these issues, we identified a thermophilic tryptophan halogenase (Th-Hal), which has significantly improved catalytic activity and stability, compared with other Fl-Hal characterised to date. When used in combination with a thermostable flavin reductase, Th-Hal can efficiently halogenate a number of aromatic substrates. X-ray crystal structures of Th-Hal, and the reductase partner (Th-Fre), provide insights into the factors that contribute to enzyme stability, which could guide the discovery and engineering of more robust and productive halogenase biocatalysts.

Subject Areas: Biology and Bio-materials, Chemistry


Instruments: I04-Macromolecular Crystallography

Documents:
c6ob01861k.pdf