Understanding High-Salt and Cold Adaptation of a Polyextremophilic Enzyme

Ram Karan, Sam Mathew, Reyhan Muhammad, Didier B. Bautista, Malvina M. Vogler, Jörg Eppinger, Romina Oliva, Luigi Cavallo, Stefan T. Arold, Magnus Rueping

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


The haloarchaeon Halorubrum lacusprofundi is among the few polyextremophilic organisms capable of surviving in one of the most extreme aquatic environments on Earth, the Deep Lake of Antarctica (−18 °C to +11.5 °C and 21–28%, w/v salt content). Hence, H. lacusprofundi has been proposed as a model for biotechnology and astrobiology to investigate potential life beyond Earth. To understand the mechanisms that allow proteins to adapt to both salinity and cold, we structurally (including X-ray crystallography and molecular dynamics simulations) and functionally characterized the β-galactosidase from H. lacusprofundi (hla_bga). Recombinant hla_bga (produced in Haloferax volcanii) revealed exceptional stability, tolerating up to 4 M NaCl and up to 20% (v/v) of organic solvents. Despite being cold-adapted, hla_bga was also stable up to 60 °C. Structural analysis showed that hla_bga combined increased surface acidity (associated with halophily) with increased structural flexibility, fine-tuned on a residue level, for sustaining activity at low temperatures. The resulting blend enhanced structural flexibility at low temperatures but also limited protein movements at higher temperatures relative to mesophilic homologs. Collectively, these observations help in understanding the molecular basis of a dual psychrophilic and halophilic adaptation and suggest that such enzymes may be intrinsically stable and functional over an exceptionally large temperature range.
Original languageEnglish (US)
Pages (from-to)1594
Issue number10
StatePublished - Oct 16 2020

Bibliographical note

KAUST Repository Item: Exported on 2020-10-23
Acknowledged KAUST grant number(s): URF/1/1976
Acknowledgements: The research reported in this publication was supported by funding from King Abdullah University of Science and Technology (KAUST) through the baseline fund and the Award No. URF/1/1976-21 from the Office of Sponsored Research (OSR). Acknowledgments: We acknowledge SOLEIL for provision of synchrotron radiation facilities, and we would like to thank L. Chavas, P. Legrand, S. Sirigu and P. Montaville for assistance in using beamline PROXIMA 1. We thank the KAUST Supercomputing Laboratory (KSL) for allowing the use the supercomputing resources. We thank the research intern, Allister Huang, for expert experimental assistance.


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