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      Structural and Chemical Biology of Terpenoid Cyclases

      review-article
      Chemical Reviews
      American Chemical Society

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          Abstract

          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.

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            Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish

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              Gibberellin biosynthesis and its regulation.

              The GAs (gibberellins) comprise a large group of diterpenoid carboxylic acids that are ubiquitous in higher plants, in which certain members function as endogenous growth regulators, promoting organ expansion and developmental changes. These compounds are also produced by some species of lower plants, fungi and bacteria, although, in contrast to higher plants, the function of GAs in these organisms has only recently been investigated and is still unclear. In higher plants, GAs are synthesized by the action of terpene cyclases, cytochrome P450 mono-oxygenases and 2-oxoglutarate-dependent dioxygenases localized, respectively, in plastids, the endomembrane system and the cytosol. The concentration of biologically active GAs at their sites of action is tightly regulated and is moderated by numerous developmental and environmental cues. Recent research has focused on regulatory mechanisms, acting primarily on expression of the genes that encode the dioxygenases involved in biosynthesis and deactivation. The present review discusses the current state of knowledge on GA metabolism with particular emphasis on regulation, including the complex mechanisms for the maintenance of GA homoeostasis.
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                Author and article information

                Journal
                Chem Rev
                Chem. Rev
                cr
                chreay
                Chemical Reviews
                American Chemical Society
                0009-2665
                1520-6890
                25 August 2017
                13 September 2017
                : 117
                : 17
                : 11570-11648
                Affiliations
                [1]Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania , 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, United States
                Author notes
                [* ]E-mail: chris@ 123456sas.upenn.edu . Tel: +1 215 898 5714.
                Article
                10.1021/acs.chemrev.7b00287
                5599884
                28841019
                ba86fa79-8d0c-4623-991c-9a71a36f3756
                Copyright © 2017 American Chemical Society

                This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.

                History
                : 20 May 2017
                Categories
                Review
                Custom metadata
                cr7b00287
                cr-2017-00287u

                Chemistry
                Chemistry

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