Enzymatic control of product distribution in terpene synthases: insights from multiscale simulations.

Current Opinion in Biotechnology
Keren RazDan Thomas Major

Abstract

In this opinion, we review some recent work on terpene biosynthesis using multiscale simulation approaches, with special focus on contributions from our group. Terpene synthases generate terpenes employing rich carbocation chemistry, including highly specific ring formations, proton, hydride, methyl, and methylene migrations, followed by reaction quenching. In these enzymes, the main catalytic challenge is not rate enhancement, but rather control of intrinsically reactive carbocations and the resulting product distribution. Herein, we review multiscale simulations of selected mono-, sesqui-, and diterpene synthases. We point to the many tools adopted by terpene synthases to achieve correct substrate fold, carbocation formation, carbocation reaction environment, and reaction quenching. A better understanding of the toolbox employed by terpene synthases is expected to aid in the search for new enzymatic and biomimetic synthetic routes to natural and unnatural terpenes.

References

Jul 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·S H NorthrupM Karplus
Nov 8, 2001·Proceedings of the National Academy of Sciences of the United States of America·M J RynkiewiczD W Christianson
Jan 24, 2002·Proceedings of the National Academy of Sciences of the United States of America·Reuben J Peters, Rodney B Croteau
Nov 15, 2002·Proceedings of the National Academy of Sciences of the United States of America·Douglas A WhittingtonDavid W Christianson
Oct 16, 2003·Journal of the American Chemical Society·Ramkumar Rajamani, Jiali Gao
Jun 7, 2005·Journal of Molecular Graphics & Modelling·Dan Thomas Major, Jiali Gao
May 4, 2006·Journal of the American Chemical Society·Pradeep Gutta, Dean J Tantillo
Jun 21, 2006·Proceedings of the National Academy of Sciences of the United States of America·Bryan T GreenhagenJoe Chappell
Sep 22, 2006·Organic Letters·Young J Hong, Dean J Tantillo
Mar 6, 2007·Journal of Computational Chemistry·H Lee WoodcockBernard R Brooks
Apr 26, 2007·Proceedings of the National Academy of Sciences of the United States of America·Meimei XuReuben J Peters
Jun 20, 2007·Nature Chemical Biology·Jonathan Gershenzon, Natalia Dudareva
Oct 9, 2007·Journal of the American Chemical Society·Rudolf K AllemannJiali Gao
Dec 7, 2007·Journal of the American Chemical Society·P Ross Wilderman, Reuben J Peters
Feb 6, 2008·Current Opinion in Chemical Biology·David W Christianson
Sep 4, 2008·Angewandte Chemie·Daniel H EssKendall N Houk
May 16, 2009·Journal of Computational Chemistry·B R BrooksM Karplus
Sep 18, 2009·Nature·Paul J Ziemann
Apr 17, 2010·Journal of the American Chemical Society·Michal Weitman, Dan Thomas Major
Feb 10, 2011·Chemical Communications : Chem Comm·Ke Zhou, Reuben J Peters
Aug 1, 2009·Nature Chemistry·Young J Hong, Dean J Tantillo
May 5, 2011·Natural Product Reports·Dean J Tantillo
Jul 1, 2011·Journal of the American Chemical Society·B Andes HessPaul E O'Maille
Aug 6, 2011·Journal of the American Chemical Society·Juan A FaraldosRudolf K Allemann
Sep 29, 2011·Nature Communications·Pamela P Peralta-YahyaTaek Soon Lee
Oct 29, 2011·Physical Chemistry Chemical Physics : PCCP·Julia Rehbein, Barry K Carpenter
Jun 30, 2012·Science·Jing-Ke WengJoseph P Noel
Aug 17, 2012·Nature·Pamela P Peralta-YahyaJay D Keasling
Oct 30, 2012·Journal of the American Chemical Society·Dan Thomas Major, Michal Weitman
Feb 27, 2013·Proceedings of the National Academy of Sciences of the United States of America·Sindy FrickAntje Burse
Apr 6, 2013·Biochemistry·Marc W van der Kamp, Adrian J Mulholland
Oct 11, 2013·Biochemistry·Marc W van der KampAdrian J Mulholland
Apr 17, 2014·Current Opinion in Chemical Biology·Dan Thomas MajorMichal Weitman
Jun 4, 2014·Angewandte Chemie·Philipp BaerJeroen S Dickschat
Feb 24, 2015·Nature Chemistry·Q Zhang, K Tiefenbacher
Jul 4, 2015·Science·Jean-Louis MagnardSylvie Baudino

❮ Previous
Next ❯

Citations

Oct 21, 2021·Chembiochem : a European Journal of Chemical Biology·Nicole G H Leferink, Nigel S Scrutton

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.