Secondary Metabolite Biosynthesis And Metabolism

This book was developed from the proceedings of the American Chemical Society, Division of Agricultural & Food Chemistry, subdivision of Natural Products Symposium "Biosynthesis and Metabolism of Secondary Natural Products" held in Atlanta, Georgia, April 1991. The objective of the conference was to bring together people from apparently diverse fields, ranging from biotechnology, metabolism, mechanistic organic chemistry, enzymology, fermentation, and biosynthesis, but who share a common interest in either the biosynthesis or the metabolism of natural products. It is our intention to help bridge the gap between the fields of mechanistic bio-organic chemistry and biotechnology. Our thanks go to Dr. Henry Yokoyama, co-organizer of the symposium, the authors who so kindly contributed chapters, the conference participants, and to those who assisted in the peer review process. We also thank the financial supporters of the symposium: ACS/AGFD, NIH General Medical Sciences, and the agricultural, pharmaceutical, biotechnology, and chromatography companies. A full list of the supporting corporations and institutions is given on the following page. Pharma-Tech and P.C., Inc. are manufacturers of instrumentation for high-speed countercurrent chromatography. We thank the Agricultural Research Service and the U. S. Department of Agriculture for granting me permission to co-organize the conference and for us to complete the book. Richard J. Petroski Susan P. McCormick USDA, ARS, National Center for Agricultural Utilization Research Peoria, IL 61604 June 10, 1992 vii CONTENTS ANTIBIOTICS Polyketide Synthetases: Enzyme Complexes and Multifunctional Proteins Directing the Biosynthesis of Bacterial Metabolites from Fatty Acids. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 . . . . . . . . . . .

This is a book about experiments and results of experiments. The results described are the fruit of thirty years' labour in the field of secondary metabolism. Secondary metabolism, more than any other part of the chemistry of life, has been the special preserve of organic chemists. Investiga tion of secondary metabolism began with curiosity about the struc tures of compounds isolated from natural sources, i.e. secondary metabolites. Coeval with structure determination there has been a curiosity about the origins and mechanism of formation of secondary metabolites (or natural products as they have been called). It is the experimental outcome of this curiosity that is described here. This account is primarily intended to be an introduction to the biosynthesis of secondary metabolites. I have also endeavoured, however, to make the book as comprehensive as possIble. This has meant that some of the material has had to be presented in abbrevi ated form. The abbreviated material is largely confined to particular sections of the book. The paragraphs marked with a dagger (t) can be omitted by the reader wishing to acquire a general introduction to the subject. A blend of the most significant and the most recent references is cited to provide the reader with ready access to the primary litera ture. This is clearly most necessary for the material presented in abbreviated form. Relevant reviews are also cited.

Life has evolved as a unified system; no organism exists similar role also has been suggested for fatty acids from alone, but each is in intimate contact with other organisms cyanolipids. Nonprotein amino acids, cyanogenic glyco and its environment. Historically, it was easier for workers sides, and the non-fatty-acid portion of cyanolipids also are in various disciplines to delimit artificially their respective incorporated into primary metabolites during germination. areas of research, rather than attempt to understand the entire Secondary metabolites of these structural types are accumu system of living organisms. This was a pragmatic and neces lated in large quantities in the seeds of several plant groups sary way to develop an understanding for the various parts. where they probably fulfill an additional function as deter We are now at a point, however, where we need to investi rents to general predation. gate those things common to the parts and, specifically, those The second type of relationship involves interaction of things that unify the parts. The fundamental aspects of many plants with other organisms and with their environment. Bio of these interactions are chemical in nature. Plants constitute logical interactions must be viewed in the light of evolution an essential part of all life systems; phytochemistry provides ary change and the coadaptation, or perhaps coevolution, of a medium for linking several fields of study.

In this new edition special mention has been made of the isolation and characterization of the enzymes of secondary metabolism; and of the new NMR techniques which have revolutionized the elucidation of biosynthetic pathways.

Plant secondary metabolism is an economically important source of fine chemicals, such as drugs, insecticides, dyes, flavours, and fragrances. Moreover, important traits of plants such as taste, flavour, smell, colour, or resistance against pests and diseases are also related to secondary metabolites. The genetic modification of plants is feasible nowadays. What does the possibility of engineering plant secondary metabolite pathways mean? In this book, firstly a general introduction is given on plant secondary metabolism, followed by an overview of the possible approaches that could be used to alter secondary metabolite pathways. In a series of chapters from various authorities in the field, an overview is given of the state of the art for important groups of secondary metabolites. No books have been published on this topic so far. This book will thus be a unique source of information for all those involved with plants as chemical factories of fine chemicals and those involved with the quality of food and ornamental plants. It will be useful in teaching graduate courses in the field of metabolic engineering in plants.

Many of the reactions and compounds involved in metabolism are almost identical in the different groups of living organisms. They are known as primary metabolic reactions and primary metabolic products. In addition, however, a wide variety of biochemical pathways are characteristic of only a few species of organisms, of single "chemical races" or even of a certain stage of differentiation of special ized cells. Such pathways are collectively referred to as "secondary metabolism", and the compounds formed are called "secondary products". Secondary products are frequently revealed by their color, smell, or taste. They are responsible for the flavor of most foodstuffs and beverages and for the color and fragrance of flowers and fruits. Many of them are part of the materia medica, e. g. , alkaloids, cardiac glycosides, antibiotics, or compounds acting as hormones. Others are used by industry, e. g. , rubber, tannins, and cellulose. This book treats the organization and significance of biosynthesis, storage, transformation, and degradation of the most important groups of secondary products in microorganisms, plants, and animals. It shows that the formation of secondary products is a common characteristic of specialized cells brought about by the action of special enzymes encoded by specific genetic material. It demon strates that the. biosynthesis of secondary products is typically without signifi cance for the individual producer cell, but may play a decisive role in the develop· ment and function of the producer organism as a whole.

Plant cell cultures are used extensively in studies of secondary metabolism, for the biosynthesis of pharmaceuticals, flavors, essences, and pigments. This book highlights recent developments in the in vitro growth of cultured plant cells and in the production of valuable secondary metabolites. Plant Cell Culture Secondary Metabolism details research on many exciting areas including:

The secondary metabolites of plants were once considered to be waste products - today, their true value is understood. New methods of separation and structural elucidation, and advances in the investigation of biochemical activities, have increased our understanding of secondary metabolites. Their function as a defense mechanisms offers a great potential for technological gain. Secondary metabolites can be utilized in agriculture to breed stronger crops and in the manufacture of biorational pesticides. They can also be exploited by medicine as theraputic agents. And these are just two of the likely uses. This landmark volume presents articles by an impressive team of experts from leading laboratories. Each chapter considers a current understanding of secondary metabolites in nature and the potential exploitation of those qualities by the biotechnology industry.