Biochemistry of the Mevalonic Acid Pathway to Terpenoids

Transcription

1 recent advances in phytochemistry volume 24 Biochemistry of the Mevalonic Acid Pathway to Terpenoids

2 RECENT ADVANCES IN PHYTOCHEMISTRY Proceedings of the Phytochemical Society of North America General Editor: Helen A. Stafford, Reed College, Portland, Oregon Recent Volumes in the Series Volume 18 Phytochemical Adaptations to Stress Proceedings of the Twenty third Annual Meeting of the Phytochemical Society of North America, Tucson, Arizona, July, 1983 Volume 19 Chemically Mediated Interactions between Plants and Other Organisms Proceedings of the Twenty-fourth Annual Meeting of the Phytochemical Society of North America, Boston, Massachusetts, July, 1984 Volume 20 Volume 21 The Shikimic Acid Pathway Proceedings of the Twenty-fifth Annual Meeting of the Phytochemical Society of North America, Pacific Grove, California, June, 1985 The Phytochemical Effects of Environmental Compounds Proceedings of the Twenty-sixth Annual Meeting of the Phytochemical Society of North America, College Park, Maryland, July, 1986 Volume 22 Volume 23 Volume 24 Opportunities for Phytochemistry in Plant Biotechnology Proceedings of the Twenty-seventh Annual Meeting of the Phytochemical Society of North America, Tampa, Florida, June, 1987 Plant Nitrogen Metabolism Proceedings of the Twenty-eighth Annual Meeting of the Phytochemical Society of North America, Iowa City, Iowa, June 1988 Biochemistry of the Mevalonic Acid Pathway to Terpenoids Proceedings of the Twenty-ninth Annual Meeting of the Phytochemical Society of North America, Vancouver, British Columbia, Canada, June 1989 A Continuation Order Plan is available for this series. A continuation order will bring delivery of each new volume immediately upon publication. Volumes are billed only upon actual shipment. For further information please contact the publisher.

3 recent advances in phytochemistry volume 24 Biochemistry of the Mevalonic Acid Pathway to Terpenoids Edited by G.H. Neil Towers University of British Columbia Vancouver, British Columbia, Canada and Helen A. Stafford Reed College Portland, Oregon PLENUM PRESS NEW YORK AND LONDON

4 Library of Congress Cataloging in Publication Data Phytochemical Society of North America. Meeting (29th: 1989: Vancouver, B.C.) Biochemistry of the Mevalonic Acid Pathway to Terpenoids 1 edited by G. H. Neil Towers and Helen A. Stafford. p. cm.-(recent advances in phytochemistry; v. 24) "Proceedings of the twenty ninth Annual meeting of the Phytochemical Society of North America, held June 16-20, 1989, in Vancouver, British Columbia, Canada" T.p. verso. Includes bibliographical references. Includes index. ISBN 978 ) ) 6 )SBN 978 ) (ebook) DO) ) O. 1007/978 ) Mevalonic acid-derivatives-synthesis-congresses. 2. Terpenes-Synthesis Congresses. 3. Botanical.chemistry-Congresses. I. Towers, G. H. Neil. II. Stafford, Helen A., III. Title. IV. Series. OK861.R38 vol. 24 [OP801.M45] '2 s-dc [581.19'2] CIP Proceedings of the Twenty-ninth Annual Meeting of the Phytochemical Society of North America, held June 16-20, 1989, in Vancouver, British Columbia, Canada 1990 Plenl,Jm Press, New York A Division of Plenum Publishing Corporation 233 Spring Street, New York, N.Y Softcover reprint of the hardcover ) st edition )990 All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher

5 PREFACE This series of lectures was delivered at the 29th meeting of the Phytochemical Society of North America, held at the University of British Columbia in Vancouver, B.C., Canada on June 16th-20th, Topics concerning terpenoids, consisting of isoprene units, are now so numerous that a judicious selection for a relatively limited symposium was difficult. We were able to assemble, however, a potpourri of reviews on topical areas of terpenoid chemistry, biochemistry and biology, by scientists who are making exciting contributions and whose work points the way to significant future research. Because of the importance of terpenoids in the life of plants, and indeed in all living organisms, a periodical review of the mevalonic acid pathway and of the subsequent biochemical events leading to the biosynthesis of isoprenoids needs no justification. Life, as we know it, would not be possible without the ability of living organisms to employ this metabolic sequence which proceeds from condensations of three molecules of acetyl-coa and terminates with the elaboration of the terpenoid precursors, isopentenyl and dimethylallyl. In addition to producing obviously essential compounds that are partially or completely of isoprenoid origin (Fig. 1), such as hormones, photosynthetic pigments, compounds involved in electron transport in respiration and in photosynthesis, oxidative enzymes and membrane components, plants elaborate thousands of novel terpenoids, many of which do not as yet have identifiable physiological, biochemical or even ecological roles, e.g. the cardenolides, ecdysones or saponins. We believe that the ecological importance for some of them, e.g., the volatile monoterpenes produced in plant trichomes serve as chemical cues for insects. Studies of the chemical signalling between plants and organisms, ranging from bacteria to mammals have expanded tremendously in recent years, and, in many cases terpenoids have been shown to be involved in these interactions.

6 vi PREFACE Mixed biosyntheses (Cn) ~r---prenylation +-Polyisoprenoids-+ (Cn) plasto-, ubi-quinones ~r----prenylation +--1 DMAPP/IPP 1- flavonoids, alkaloids, nucleic acid bases, coumarins, proteins benzoquinones t 1PP1 1 ~ prenylation.. GPP /NPP (CIO ) monoterpenes benzo- & naphtha-quinones, alkaloids, flavonoids, IPP cannabinoids Pure isoprenoids gutta rubber polyprenols isoprene iridoids pseuoalkaloids l prenylation lfpp):(c15) sesqu~~~;;~:: porphyrins IPP abscisic acid resterification... I-----GGPP porphyrins DMAPP IPP GPP NPP FPP GGPP GFPP dimethy1ally1 isopenteny1 gerany1 nery1 farnesy1 geranyigerany1 gerany1farnesy1 IPP FPP GGPP (C30) sterols, brassins saponins, cardenolides pseudoalkaloids (C20) gibberellins pseudoalkaloids carotenoids GFPP (C25) sesterterpenes Fig. 1. Some Products of the Mevalonate Pathway in Plants

7 PREFACE The sheer number of new terpenes and terpenoids, most of which of course bear trivial chemical names, in terrestrial and marine plants, presents an increasing problem for the phytochemist; surely it is time for the development of a new system that will allow for easy information retrieval in studies of the biochemical and biological relationships of these ever increasing families of phytochemicals. Professor Fischer points out (Chapter 4) that, in the ten years between 1979 and 1989, the number of identified sesquiterpene lactones alone rose from 500 to over 3200! In Chapter 1 Bach and his colleagues present an up-todate analysis of the biochemistry of the mevalonic acid (MVA) pathway, particularly the properties of hydroxymethylglutaryl CoA reductase (HMGR). Included in this chapter is a complete discussion of the currently conflicting views of compartmentalization of the enzymes involved and of regulation. They also discuss the potent fungal terpenoids, e.g. mevinolin, which are specific inhibitors of HMGR and which have been shown, by them, to act as growth inhibitors. These compounds are in current use in preventive medicine in reducing cholesterol biosynthesis. In Chapter 2 Boronat and his colleagues give us a close look at the structure of HMGR as well as aspects of its molecular biology. In spite of the large number of monoterpenes in plants, many of which, e.g. camphor, have been known as plant constituents for over a hundred years, it was not until the pioneering investigations of Croteau's group, in the last decade or so, that an understanding of the nature of the cyclases, or enzymes yielding mono- and bicyclic terpenes from geranyl- or neryl- pryophosphates, was achieved. Gershenzon and Croteau provide the most complete account to date of the enzymology, regulation, compartmentalization, subcellular regulation and metabolism of monoterpenes. The results described should encourage plant physiologists to study the transport and further metabolism of this large class of terpenoids. Fischer discusses the possible biochemical relationships of the fifteen or more classes of sesquiterpene lactones, inviting enzymologists to explore this vast area. It is a sad reflection on plant biochemists that not a single enzyme is known with regard to these compounds. In Chapter 5, Phinney and Spray pay particular attention to the pathway from GA12-

8 viii PREFACE aldehyde to the Cl9 gibberellins, with emphasis on the early- 13-hydroxylation pathway leading to the hormone gibberellin (GAl). Plant anti-microbial terpenoids are discussed by West and his colleagues, who provide a stimulating account of diterpene phytoa1exins in soybeans and in rice tissue cultures with particular emphasis on regulation of their biosynthesis. The potential for studies of terpene biochemistry and molecular biology are clearly evident in these studies. Isman, Proksch and Clark provide an opening to chemical ecology with a clear report on the insecticidal terpenoids of the American composites of the genus Encelia. These conspicuous plants of the Baja and other arid lands of Mexico and the U.S.A. excrete copious amounts of resins whose bioactivities were initially studied by Rodriguez's group in California. Many possibilities for plant/insect studies at a chemical level become evident in this chapter. In Chapter 8, by Andersen et al., we are introduced to the novel chemistry of a small selection of the 1700 or more new terpenoids identified in the 1980's in marine hydroids, sponges, nudibranchs and algae. Here again is an invitation for exciting work in chemical ecology. The final chapter by Nes is a novel and perhaps highly controversial look at the world of sterols. It includes much food for thought about one of the most intriguing and still poorly understood groups of natural products. We wish to thank all those who helped to arrange this meeting, all of the speakers and those who presented posters. The generous support of the Natural Sciences and Engineering Council of Canada was greatly appreciated. We hope that the reader will enjoy this addition to our annual symposium series. We believe that it will provide much interesting reading about a very large group of natural products. February, 1990 G.H.N. Towers H.A. Stafford

9 CONTENTS Some Properties of Enzymes Involved in the Biosynthesis and Metabolism of 3-Hydroxy-3- methylglutararyl-coa in Plants.... Thomas J. Bach, Thomas Weber, and Anja Motel Molecular Cloning and Characterization of Plant 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase... M. Monfar, C. Caelles, L. Balcells, A. Ferrer, F.G. Hegardt, and A. Boronat Regulation of Monoterpene Biosynthesis in Higher Plants.... Jonathan Gershenzon and Rodney Croteau Sesquiterpene Lactones: Biogenesis and Biomimetic Tranformations Nikolaus H. Fischer 5. Plant Hormones and the Biosynthesis of Gibberellins: The Early-13-Hydroxylation Pathway Leading to GAl Bernard o. Phinney and Clive R. Spray 6. Diterpenoid Phytoalexins: Biosynthesis and Regulation Charles A. West, Augusto F. Lois, Karen A. Wickham, and ~ue-ying Ren 7. Terpenoid Anti-herbivore Chemistry of Encelia Species (Asteraceae) Murray B. Isman, Peter Proksch, and Curtis Clark 8. Terpenoids from Selected Marine Invertebrates Raymond J. Andersen, E. Dilip de Silva, Eric J. Dumdei, Peter T. Northcote, Charles Pathirana, and Mark Tischler ix

10 x CONTENTS 9. Control of Sterol Biosynthesis and Its Importance to Developmental Regulation and Evolution W. David Nes Index 329