title: Expanding the Halohydrin Dehalogenase Enzyme Family: Identification of Novel Enzymes by Database Mining.
abstract: Halohydrin dehalogenases are very rare enzymes that are naturally involved in the mineralization of halogenated xenobiotics. Due to their catalytic potential and promiscuity, many biocatalytic reactions have been described that have led to several interesting and industrially important applications. Nevertheless, only a few of these enzymes have been made available through recombinant techniques; hence, it is of general interest to expand the repertoire of these enzymes so as to enable novel biocatalytic applications. After the identification of specific sequence motifs, 37 novel enzyme sequences were readily identified in public sequence databases. All enzymes that could be heterologously expressed also catalyzed typical halohydrin dehalogenase reactions. Phylogenetic inference for enzymes of the halohydrin dehalogenase enzyme family confirmed that all enzymes form a distinct monophyletic clade within the short-chain dehydrogenase/reductase superfamily. In addition, the majority of novel enzymes are substantially different from previously known phylogenetic subtypes. Consequently, four additional phylogenetic subtypes were defined, greatly expanding the halohydrin dehalogenase enzyme family. We show that the enormous wealth of environmental and genome sequences present in public databases can be tapped for in silico identification of very rare but biotechnologically important biocatalysts. Our findings help to readily identify halohydrin dehalogenases in ever-growing sequence databases and, as a consequence, make even more members of this interesting enzyme family available to the scientific and industrial community.
authors.affiliation: Junior Professorship for Biocatalysis, Institute of Biotechnology, RWTH Aachen University, Aachen, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Schallmey
authors.affiliation: Junior Professorship for Biocatalysis, Institute of Biotechnology, RWTH Aachen University, Aachen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Koopmeiners
authors.affiliation: Junior Professorship for Biocatalysis, Institute of Biotechnology, RWTH Aachen University, Aachen, Germany.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Wells
authors.affiliation: Enzymicals AG, Greifswald, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Wardenga
authors.affiliation: Junior Professorship for Biocatalysis, Institute of Biotechnology, RWTH Aachen University, Aachen, Germany a.schallmey@biotec.rwth-aachen.de.
authors.forename: Anett
authors.identifier: http://orcid.org/0000-0002-6670-0574
authors.initials: A
authors.lastname: Schallmey
mesh_terms: D001419:Bacteria / Q000201:enzymology*; D003001:Cloning, Molecular; D016000:Cluster Analysis; D019295:Computational Biology; D057225:Data Mining; D015870:Gene Expression; D014644:Genetic Variation; D006867:Hydrolases / Q000235:genetics* / Q000378:metabolism*; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid
chemical_list: D006867:Hydrolases; C430848:halohydrin dehalogenase