Table Of Contentrecent advances in phytochemistry
volume 24
Biochemistry of the
Mevalonic Acid Pathway
to Terpenoids
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 The Shikimic Acid Pathway
Proceedings of the Twenty-fifth Annual Meeting of
the Phytochemical Society of North America, Pacific Grove,
California, June, 1985
Volume 21 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 Opportunities for Phytochemistry in Plant Biotechnology
Proceedings of the Twenty-seventh Annual Meeting of the Phytochemical
Society of North America, Tampa, Florida, June, 1987
Volume 23 Plant Nitrogen Metabolism
Proceedings of the Twenty-eighth Annual Meeting of the Phytochemical
Society of North America, Iowa City, Iowa, June 1988
Volume 24 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
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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
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·)·4684·879)·6 )SBN 978·)·4684·8789·3 (eBook)
DO) ) O. 1007/978·)·4684·8789·3
1. Mevalonic acid-Derivatives-Synthesis-Congresses. 2. Terpenes-Synthesis
Congresses. 3. Botanical.chemistry-Congresses. I. Towers, G. H. Neil. II. Stafford,
Helen A., 1922- . III. Title. IV. Series.
OK861.R38 vol. 24
[OP801.M45]
581.19'2 s-dc20 90-7265
[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. 10013
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
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, 1989. 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
pyrophosphate and dimethylallyl pyrophosphate. 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.
vi PREFACE
Mixed biosyntheses Pure isoprenoids
(Cn)
~r---prenYlation +-Polyisoprenoids-+ (Cn) gutta rubber
t polyprenols
plasto-, ubi-quinones
+--1 1-
~r----prenYlation DMAPP/IPP isoprene
flavonoids, alkaloids,
1PP1
nucleic acid bases,
coumarins, proteins
benzoquinones 1
~ prenylation .. GPP /NPP ---... (CIO) monoterpenes
iridoids
benzo- & naphtha-quinones, pseuoalkaloids
alkaloids, flavonoids, ---IP-P l
cannabinoids
l prenylation ...... FPP ):(C15) sesqu~~~;;~::
porphyrins IPP abscisic acid
(C30)
sterols, brassins
FPP saponins, cardenolides
pseudoalkaloids
resterification ......I -----GGPP
porphyrins
(C20) gibberellins
pseudoalkaloids
IPP
DMAPP dimethy1ally1 carotenoids
pyrophosphate
IPP isopenteny1 GGPP
pyrophosphate
GPP gerany1 GFPP ----.... (C25) sesterterpenes
pyrophosphate
NPP nery1
pyrophosphate
FPP farnesy1
pyrophosphate
GGPP geranyIgerany1
pyrophosphate
GFPP gerany1farnesy1
pyrophosphate
Fig. 1. Some Products of the Mevalonate Pathway in Plants
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-to
date 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-
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
CONTENTS
1. Some Properties of Enzymes Involved in the
Biosynthesis and Metabolism of 3-Hydroxy-3-
methylglutararyl-CoA in Plants .................... . 1
Thomas J. Bach, Thomas Weber, and Anja Motel
2. Molecular Cloning and Characterization of Plant
3-Hydroxy-3-methylglutaryl Coenzyme A Reductase .... 83
M. Monfar, C. Caelles, L. Balcells,
A. Ferrer, F.G. Hegardt, and A. Boronat
3. Regulation of Monoterpene Biosynthesis in Higher
Plants ............................................ . 99
Jonathan Gershenzon and Rodney Croteau
4. Sesquiterpene Lactones: Biogenesis and Biomimetic
Tranformations .................................... 161
Nikolaus H. Fischer
5. Plant Hormones and the Biosynthesis of
Gibberellins: The Early-13-Hydroxylation Pathway
Leading to GAl .................................... 203
o.
Bernard Phinney and Clive R. Spray
6. Diterpenoid Phytoalexins: Biosynthesis
and Regulation. . . .. . .. . .. . .. . . . .. . . . .. . .. . . . . .. . . .. 219
Charles A. West, Augusto F. Lois,
Karen A. Wickham, and ~ue-Ying Ren
7. Terpenoid Anti-herbivore Chemistry of Encelia
Species (Asteraceae) ............................... 249
Murray B. Isman, Peter Proksch, and
Curtis Clark
8. Terpenoids from Selected Marine Invertebrates ...... 265
Raymond J. Andersen, E. Dilip de Silva,
Eric J. Dumdei, Peter T. Northcote, Charles
Pathirana, and Mark Tischler
ix
x CONTENTS
9. Control of Sterol Biosynthesis and Its Importance
to Developmental Regulation and Evolution ......... 283
W. David Nes
Index 329
