Alcohol dehydrogenase from Red Sea brine pool

[155] Groetzinger S., Karan R., Strillinger E., Bader S., Frank A., Al Rowaihi I., Wackerow W., Akal A., Archer J., Rueping M., Weuster-Botz D., Groll M., Eppinger J., Arold S.
Identification and experimental characterization of an extremophilic brine pool alcohol dehydrogenase from single amplified genomes
ACS Chem. Biol., 2018, 13, 161-70, PDF

Because only 0.01% of prokaryotic genospecies can be cultured and in situ observations are often impracticable, cultureindependent methods are required to understand microbial life and harness potential applications of microbes. Here, we report a methodology for the production of proteins with desired functions based on single amplified genomes (SAGs) from unculturable species. We use this method to resurrect an alcohol dehydrogenase (ADH/D1) from an uncharacterized halo-thermophilic archaeon collected from a brine pool at the bottom of the Red Sea. Our crystal structure of 5,6-dihydroxy NADPHbound ADH/D1 combined with biochemical analyses reveal the molecular features of its halo-thermophily, its unique habitat adaptations, and its possible reaction mechanism for atypical oxygen activation. Our strategy offers a general guide for using SAGs as a source for scientific and industrial investigations of “microbial dark matter.”