5lv9

Publication Abstract from PubMed

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.

Structure and biocatalytic scope of thermophilic flavin-dependent halogenase and flavin reductase enzymes.,Menon BR, Latham J, Dunstan MS, Brandenburger E, Klemstein U, Leys D, Karthikeyan C, Greaney MF, Shepherd SA, Micklefield J Org Biomol Chem. 2016 Oct 4;14(39):9354-9361. PMID:27714222^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.