David W. Christianson

The year 2017 marks the twentieth anniversary of terpenoid cyclase structural biology: a trio of terpenoid cyclase structures reported together in 1997 were the first to set the foundation for understanding the enzymes largely responsible for the exquisite chemodiversity of more than 80000 terpenoid natural products. Terpenoid cyclases catalyze the most complex chemical reactions in biology, in that more than half of the substrate carbon atoms undergo changes in bonding and hybridization during a single enzyme-catalyzed cyclization reaction. The past two decades have witnessed structural, functional, and computational studies illuminating the modes of substrate activation that initiate the cyclization cascade, the management and manipulation of high-energy carbocation intermediates that propagate the cyclization cascade, and the chemical strategies that terminate the cyclization cascade. The role of the terpenoid cyclase as a template for catalysis is paramount to its function, and protein engineering can be used to reprogram the cyclization cascade to generate alternative and commercially important products. Here, I review key advances in terpenoid cyclase structural and chemical biology, focusing mainly on terpenoid cyclases and related prenyltransferases for which X-ray crystal structures have informed and advanced our understanding of enzyme structure and function.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructural Biology and Chemistry of the Terpenoid CyclasesDavid W. ChristiansonView Author Information Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323 Cite this: Chem. Rev. 2006, 106, 8, 3412–3442Publication Date (Web):June 1, 2006Publication History Received21 October 2005Published online1 June 2006Published inissue 1 August 2006https://pubs.acs.org/doi/10.1021/cr050286whttps://doi.org/10.1021/cr050286wresearch-articleACS PublicationsCopyright © 2006 American Chemical SocietyRequest reuse permissionsArticle Views8640Altmetric-Citations645LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Anions,Cyclization,Hydrocarbons,Monomers,Peptides and proteins Get e-Alerts

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCarboxypeptidase ADavid W. Christianson and William N. LipscombCite this: Acc. Chem. Res. 1989, 22, 2, 62–69Publication Date (Print):February 1, 1989Publication History Published online1 May 2002Published inissue 1 February 1989https://pubs.acs.org/doi/10.1021/ar00158a003https://doi.org/10.1021/ar00158a003research-articleACS PublicationsRequest reuse permissionsArticle Views2569Altmetric-Citations579LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts