Squalene-hopene cyclases: evolution, dynamics and catalytic scope
2016 (English)In: Current opinion in structural biology, ISSN 0959-440X, E-ISSN 1879-033X, Vol. 41, 73-82 p.Article in journal (Refereed) Published
Herein we highlight recent mechanistic findings on the impact of solvent dynamics on catalysis displayed by squalene-hopene cyclases (SHCs). These fascinating biocatalysts that appeared early during the evolution of terpene biosynthetic machineries exploit a catalytic aspartic acid donating the anti-oriented proton to the terminal C. C double bond of pre-folded isoprenoid substrates. We review how the unusual strength of this Brønsted acid can be used to harness a plethora of non-natural protonation-driven reactions in a plastic enzyme fold. Moreover, recent results underline how the reaction termination by deprotonation or water addition is governed by the spatial location of water in the active site. Site-directed mutagenesis of amino acids located in the hydrophobic binding pocket allows for the generation of novel catalytic function by active site reshaping with relatively small enzyme libraries. A deepened understanding of triterpene cyclase dynamics in concert with chemical expertise thus have a great potential to allow for the biocatalytic manufacturing of tailored building bricks that would expand the chemical repertoire currently found in nature.
Place, publisher, year, edition, pages
Elsevier, 2016. Vol. 41, 73-82 p.
bacterial enzyme, lyase, squalene hopene cyclase, triterpene cyclase, unclassified drug, Alicyclobacillus acidocaldarius, binding site, catalysis, chemical bond, chemical structure, enzyme active site, hydrophobicity, molecular dynamics, molecular evolution, molecular library, nonhuman, priority journal, protein expression, proton transport, Review, site directed mutagenesis
IdentifiersURN: urn:nbn:se:kth:diva-195188DOI: 10.1016/j.sbi.2016.05.019ScopusID: 2-s2.0-84975488849OAI: oai:DiVA.org:kth-195188DiVA: diva2:1051671
FunderScience for Life Laboratory - a national resource center for high-throughput molecular bioscienceSwedish Research Council, 621-2013-5138
QC 201612022016-12-022016-11-022016-12-02Bibliographically approved