Natural Products from Plants Second Edition Copyright 2006 by Taylor & Francis Group, LLC Natural Products from Plants Second Edition Leland J. Cseke Ara Kirakosyan Peter B. Brielmann Copyright 2006 by Taylor & Francis Group, LLC 2976_Discl.fm Page 1 Friday, January 6, 2006 11:00 AM Published in 2006 by CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2006 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group No claim to original U. Government works Printed in the United States of America on acid-free paper 10 9 8 7 6 5 4 3 2 1 International Standard Book Number-10: 0-8493-2976-0 (Hardcover) International Standard Book Number-13: 978-0-8493-2976-0 (Hardcover) Library of Congress Card Number 2005056059 This book contains information obtained from authentic and highly regarded sources.
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Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Library of Congress Cataloging-in-Publication Data Natural products from plants / Leland J. Includes bibliographical references and index.6'3--dc22 2005056059 Visit the Taylor & Francis Web site at http://www.com Taylor & Francis Group and the CRC Press Web site at is the Academic Division of Informa plc.com Copyright 2006 by Taylor & Francis Group, LLC 2976_C000.fm Page v Wednesday, May 31, 2006 10:09 AM Dedication We dedicate this book to Steven F., the first Gayle Halperin Kahn Professor of Integrative Medicine at the University of Michigan, as well as all the other pioneering individuals who have devoted their lives to the study, application, and conservation of plants. Copyright 2006 by Taylor & Francis Group, LLC 2976_C000.fm Page vii Wednesday, May 31, 2006 10:09 AM Preface As a result of teaching many undergraduate and graduate students about plant natural products in a wide range of plant biology courses, the need for a comprehensive yet thorough collection of information on what kinds of natural products plants produce, including why they produce them, became very apparent.
Currently, such information is contained within thousands of somewhat disjointed reports about the helpful qualities and toxic effects of different plant species throughout the world. The aim of this second edition of the book is to help bring more unity and understanding to this complicated and often contradictory jumble of information. We updated and revised previously presented information and added more than 50% new topics that deal with plant natural product biochemistry, biotechnology, and molec- ular biology, as well as new separation techniques and bioassays. This book is useful to many, including biochemists, natural product chemists, pharmacologists, pharmacists, and molecular biologists; research investigators in industry, federal labs, and universities; physicians, nurses, nurse practitioners, and practitioners of integrative medicine; premedical and medical students; ethnobotanists, ecologists, and conservationists; nutritionists; organic gardeners and farmers; those interested in herbs and herbal medicine; and even lawyers.
With the growing interest in this field by professionals and the general public alike, it was important for us to produce a book that encompasses as much information as possible on the natural products produced by plants as well as their importance in today’s world. We hope that this book helps to meet this need. Some of the most compelling reasons for writing a book on natural products in plants include the following: • While there has been a great deal of progress made in understanding plant natural products, a general lack of knowledge and much misinformation remain about natural products in plants and their uses by people. • Many of the natural products in plants of medicinal value offer us new sources of drugs that have been used effectively for centuries in traditional medicine.
Many compounds used in medicine today have original derivatives that were of plant origin. • Plants are sources of poisons, addictive drugs, and hallucinogens. These have importance in human medicine and in human social action and behavior. • Many people are interested in using natural products from plants for preventive medicine, but these people must be made aware of potential harmful effects of such compounds.
• Plants provide us with thousands of novel compounds that give us medicines, fragrances, flavorings, dyes, fibers, foods, beverages, building materials, heavy metal chelators important in bioremediation, biocides, and plant growth regulators. • Knowledge about how and why plants produce such a vast array of metabolites gives us new insights into how plants use these compounds to deter predators and pathogens, attract and deter pollinators, prevent other plants from competing with themselves for the same resources, and defend themselves against environmental stress. This book was organized to provide relevant and practical information on each of the above topics. It begins with a discussion of the various types of compounds found in plants (Chapter 1).
We then discuss how and why these compounds are made by plants (Chapter 2). In Chapter 3, we consider how the synthesis of these compounds is regulated by environmental stresses, biotic factors, biochemical regulators, and gene expression to provide a better understanding of how these compounds benefit the plants themselves. Seven new chapters following Chapter 3 were added in this new edition of the book: Chapter 4 provides information about plant natural products in the rhizosphere (plant root–soil interface Copyright 2006 by Taylor & Francis Group, LLC 2976_C000.fm Page viii Wednesday, May 31, 2006 10:09 AM regions). Chapter 5 covers examples of the molecular biology of natural products.
In Chapter 6, we discuss natural product biosynthesis in the pregenomics and genomics eras. A new Chapter 7 deals with plant biotechnology for the production of natural products. Chapters 8, 9, and 10, respectively, guide the reader through analytical and preparative separations of natural products, how natural products are characterized, and bioassays for activity of natural products. In Chapter 11, we discuss the modes of action of natural products at target sites, using classic examples from medicine and cell biology.
Chapter 12 includes information on the uses of plant natural products by humans and the risks associated with their use. The principle of synergy between separate kinds of compounds from a single plant source and from more than one plant source is discussed in Chapter 13. Chapter 14 takes a global view of various strategies that are used to conserve plants that produce natural products of value to humans. Finally, in a new Chapter 15, we address the relationship between people and plants.
The individual chapters of this book are organized according to the following format: chapter title, chapter outline, introduction to the chapter, chapter topics and text, conclusions (take-home lessons), and references cited for further reading. In addition, some of the chapters contain boxed essays written by experts in the field to bring diversity to the topics. We chose this format in order to aid the reader in comprehending the material and to stimulate one to probe the chapter topics further. The Appendix to this book (“Information Retrieval on Natural Products in Plants”) helps one to embark on the latter endeavor.
Regarding terminology pertaining to plant metabolites, we often encounter the terms “primary metabolite” and “secondary metabolite” in the literature. Traditionally, primary metabolite refers to nucleic acids, amino acids, proteins, lipids, carbohydrates, and various energetic compounds falling within the primary metabolic pathways of each cell. These compounds are essential for plant growth, development, reproduction, and survival. Secondary metabolite is a term that was originally coined to describe compounds that were not thought, at the time, to be essential to plant function.
This old idea, however, cannot be defended on strictly chemical grounds, because, apparently, all natural products produced by plants have some survival value to the plant. Thus, the modern use of the term “secondary metabolite” typically refers to those compounds of low molecular weight that are often restricted to specific plant families and genera. These compounds may be important for pollination, attraction and deterrence of predators, or defense against pathogenic fungi and bacteria, or they may be essential for plant survival in stressful environments. In this book, we attempt to avoid the terminology of “primary” and “secondary” by using simply “metabolite,” “product,” or “compound” wherever possible.
However, because the traditional terms “primary metabolite” and “secondary metabolite” are still used widely in the literature as acceptable terminology, we continue to use them when we refer to “secondary metabolism” in the traditional sense (see Chapters 4, 6, and 7 for examples). Copyright 2006 by Taylor & Francis Group, LLC 2976_C000.fm Page ix Wednesday, May 31, 2006 10:09 AM The Editors Leland J., earned a doctorate in plant cellular and molecular biology through the Depart- ment of Molecular, Cellular, and Developmental Biology at the University of Michigan, Ann Arbor. His dissertation research included the molecular biology, evolution, and biotechnological applications of terpenoid scent compound production in Clarkia and Oenothera species in the laboratory of Dr. Cseke is a research assistant professor in the Department of Biological Sciences at the University of Alabama, Huntsville, where he works in conjunction with Dr.
Podila in a large team effort to determine the molecular mechanisms of keystone species in forest ecosystem responses to environmental perturbations. The DOE-funded project represents an “Integrated Functional Genomics Consortium to Increase Carbon Sequestration in Poplar Trees” through the study of aspen Free-Air Carbon dioxide Enrichment (aspen FACE research). In addition, Dr. Cseke investigates the activity of aspen (Populus tremuloides) MADS-box genes in wood development.
Cseke spent several years as a research assistant professor at Michigan Technological University working to discover the functionality of floral-specific MADS-box genes in aspen flower development. Cseke was also a postdoctoral fellow in the Department of Plant Sciences at the University of Arizona in the laboratory of Dr. There, he worked to elucidate the factors involved in functional sense and antisense suppression of genes involved in anthocyanin biosynthesis. Cseke’s interests include the biosynthesis of plant chemical products, their uses by humans, and the study of the global effects of transgenes on plant metabolism.
This led to his coauthoring the first edition of Natural Products from Plants (CRC Press, 1999). In addition, Dr. Cseke has done some work in the study of possible methods for improving separation and enhancing the biosynthesis of the cancer-fighting diterpene, taxol, in Taxus species in the laboratory of Dr. Peter Kaufman, and his knowledge of such subjects has been directed toward the teaching of classes emphasizing biotechnology and the chemical principles of biology.
Ara Kirakosyan, Ph., is associate professor of biology at Yerevan State University, Armenia, and is currently research investigator at the University of Michigan Integrative Medicine program (UMIM). He received a Ph. in molecular biology from Yerevan State University, Armenia in 1993. His research fields focus on the phytochemistry and molecular biology of medicinal plants.
His research interests include plant cell biotechnology to produce enhanced levels of medicinally important secondary metab- olites, and metabolic engineering based on the integration of functional genomics, metabolomics, tran- scriptomics, and large-scale biochemistry. He carried out postdoctoral research in the Department of Pharmacognosy at Gifu Pharmaceutical University, Gifu, Japan, under the supervision of Prof.