Herbicide Classes in Development: Mode of Action, Targets, Genetic Engineering, Chemistry

373 Pages·2002·8.01 MB·English

by  Tsutomu Shimizu

Peter Boger· Ko Wakabayashi· Kenji Hirai {Eds.}
Herbicide Classes in Development
Springer
Berlin
Heidelberg
New York
Barcelona
Hong Kong
London
Milan
Paris
Tokyo
Peter Boger· Ko Wakabayashi· Kenji Hirai {Eds.}
Herbicide Classes
in Development
Mode of Action, Targets,
Genetic Engineering, Chemistry
With 96 Figures, 2 in Color, and 53 Tables
Springer
Professor Dr. PETER BOGER
University of Konstanz
Department of Plant Physiology and Biochemistry
D-78457 Konstanz
Germany
Professor Dr. Ko WAKABAYASHI
Tamagawa University
Department of Physiology and Biochemistry
Machida-shi, Tokyo 194-8610
Japan
Dr. KENJI HIRAI
Sagami Chemical Research Center
Hayakawa 2743-1, Ayase
Kanagawa 252-1193
Japan
ISBN-13:978-3-642-63972-2 Springer-Verlag Berlin Heidelberg New York
Library of Congress Cataloging-in-Publication Data
Herbicide classes in development : mode of action, targets, genetic engineering,
chemistry I Peter Boger, Ko Wakabayashi, Kenji Hirai (eds.).
p. cm.
Includes bibliographical references.
ISBN-13: 978-3-642-63972-2 e-ISBN-13:978-3-642-59416-8
DOl: 10.1007/978-3-642-59416-8
1. Herbicides. 2. Herbicide-resistant crops. L Boger, Peter. II. Wakabayashi, K. (Ko),
1938- III. Hirai, Kenji, 1953-
SB951.4 .H425 2002
632'.954 - dc21 2002070471
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Preface
Chemical pest control is in use in practically every country in the world since
agrochemicals play a decisive role in ensuring food supply and protection
against damage by pests, insects and pathogenic fungi. Particularly in the half
century since World War II, food production has risen dramatically in most
parts of the world. In the last 20 years, the yield of major crops has roughly
doubled in Western agriculture and there is still the potential for further
achievements, particularly in the developing countries.
The world's cereal and rice production, now more than 2 billion tons/year,
has to increase by 2.4% annually to cope with the rising food demand caused
mainly by the growing population and improvement of living standards in
most of the developing countries. Such a demand for food has to be achieved
by higher yields from the restricted arable land already in use. Global farm
land resources are about 1.4 billion ha, of which 1.2 billion ha is cultivated with
major crops. Experts agree that a future substantial addition of new produc
tive areas is unlikely. Those with a high yield potential are already in use; new
fields with a lower output may possibly be obtained by cultivation of arid or
cold areas. More recently, new areas of large-scale farmland have been devel
oped in tropical regions of Latin America, primarily in Argentina and Brazil,
at the cost of the destruction of tropical rain forest.
The 1980s were an exciting period for the development of modern herbi
cides, for both industry and academia. Acetolactate synthase (ALS) inhibitors,
represented by the sulfonylurea (SU) and imidazolinone (lMI) classes, were
introduced into chemical weed control. The start of the widespread use of
new acetyl-CoA carboxylase (ACCase) inhibitors such as the phenoxypro
pionate and cyclohexanedione classes brought about a major turning
point in the subsequent evolution of agrochemicals. The discovery of fiuoro
modified tetrahydrophthalimides as PPO (= protoporphyrinogen oxidase,
Protox) inhibitors, such as fiumiclorac-pentyl, is another breakthrough in the
explosive development of the next-generation of cyclic imide classes. These
new herbicide chemistries, which combine excellent activity with unparalleled
lower dosage, crop safety, specific mechanism of action and/or structural
high novelty, have been rapidly adopted worldwide and have had an amazing
impact on agriculture.
Today, the use rate of modern herbicides is in the range of 100-300ga.i.lha,
with a declining tendency. In particular, the very low use rates of original SU
and cyclic imide herbicides have prompted agrochemical researchers to find
VI Preface
more highly active compounds, which has led to successive discoveries of as
many as 39 kinds of new ALS-inhibiting herbicides, including the triazolopy
rimidines and pyrimidyloxybenzoates, and no less than 18 new cyclic imide
classes of PPO inhibitors in the 1990s. The chemistry of these ALS and PPO
herbicides has been the most dynamic area of research in the past 20 years.
The latest phenoxypropionate ACCase inhibitors are applied in the range of
100-150ga.i.!ha and SU and cyclic imide herbicides require an even lower
amount, down to 5ga.i.!ha for some commercially active ingredients. Obvi
ously, soil overloading with chemicals or leaching problems is not an issue with
such low application doses.
To date, more than 400 herbicides have been registered, or are in the regis
tration process, and these form the active ingredients of thousands of com
mercial products. Among the registered herbicides whose modes of action are
currently understood, 269 kinds of herbicides are used around the world and
these are categorized according to their target sites, modes of action, similar
ity of induced symptoms or chemical classes by the Herbicide Resistance
Action Committee (HRAC) in cooperation with the Weed Science Society of
America (WSSA).
About ten enzymatic herbicide targets have been characterized in detail,
some more may be determined by mode of action studies in the future. Accord
ingly, the mainstream of herbicide investigation is the search for and synthe
sis of new structures acting upon these known targets. Therefore, this book
should update the state of target-oriented research by dealing with the follow
ing topical herbicide classes: (1) ALS inhibitors, (2) carotenogenesis inhibitors
(bleaching herbicides), (3) inhibitors of aromatic amino acid biosynthesis
(glyphosate), (4) inhibitors of glutamine synthetase (glufosinate), (5) ACCase
inhibitors, (6) inhibitors of very long-chain fatty acid biosynthesis, (7) cellu
lose biosynthesis inhibitors, and (8) PPO (or Protox) inhibitors. This book
presents timely physiological and biochemical information on those inhibitors
and herbicide classes which are the focus of today's research and development.
For example, auxin-type compounds and photosynthesis inhibitors are not
dealt with.
Each of the first eight chapters covers, at least in part, the relevant aspects
relating to symptoms of herbicidal activity, mode of action to provide a ratio
nal approach for weed resistance management, biochemical characteristics of
the target enzyme, model assays and cell-free biochemical tests to obtain quan
titative phytotoxic inhibition data for larger compound series, and molecular
genetics of the herbicide target(s) with special reference to transformed
inhibitor-resistant plants.
Development of transgenic herbicide-resistant crops is a strong issue today
and will grow in importance. Therefore, Chapter 9, in particular, outlines the
methods of how a plant is transformed and a resistant crop is developed,
describing the cloning of gene(s), complementation, vector constructs, PCR
mediated gene mutation, selection, and crossings. An extended Chapter 10
provides agrochemical characteristics and major synthetic routes of the typical
Preface VII
herbicides cited in Chapters 1-8. Structural evolutions of the inhibitor/herbi
cide classes belonging to these chapters are chronologically reviewed from
the viewpoint of molecular design by illustrating representative compounds
for the last decade. However, only some new synthetic pathways for Protox
inhibitors will be documented since detailed information up to 1997 has been
reviewed in Peroxidizing Herbicides, published by Springer in 1999.
Many herbicides and synthetic compounds interfering with plant metabo
lism exist as optical isomers exhibiting specific phytotoxic or regulatory
activities. The R-form of phenoxypropionate ACCase inhibitors is far more
active than the S-isomer. In contrast, the S-forms of dimethenamid or meto
lachlor are active, but not the R-form. In addition, glufosinate and bialaphos,
produced by fermentation, are optically active compounds and their racemic
isomers are less inhibitory. Accordingly, Chapter 11 outlines prominent exam
ples, their enantioselective synthesis and general biological activity. Chapter
12 deals with new considerations on transcuticular penetration based on
quantitative analysis of its kinetics by a logistic-kinetic model. The last chapter
relates the findings presented in Chapter 6 on chloroacetamides and function
ally equivalent novel structures focusing on structure-activity relationships.
These are based on herbicidal greenhouse activity and quantitative inhibition
of cell-free microsomal fatty-acid elongation.
There is a continuous need for new active ingredients. Changes in agricul
tural politics, occurrence of herbicide-resistant species and changing toxico
logical and environmental fate requirements demand the development of more
effective, more selective and environmentally benign herbicides. It is believed
that members of the modern herbicide classes covered in this volume fulfill
these requests. No volume presenting a combination of synthetic chemistry
with herbicide physiology, biochemistry and engineered resistance, compa
rable to the format outlined here, has yet been published. Treatises on the mode
of action of herbicide classes included in the present chapters are almost 10
years old. A demand for this book by herbicide researchers can be safely
assumed. We also believe that the contributions should be a valuable resource
for established colleagues working on plant protection, and for advanced stu
dents of organic and agricultural chemistry, as well as plant biochemistry.
Finally, it is hoped that readers will be stimulated by the information and mes
sages presented. They may help to further develop integrated weed manage
ment practices that deliver a sustained food crop production.
In writing this volume, the editors thank the authors for their outstanding
contributions and for making their expertise available. They are also grateful
for the help and advice of many colleagues, including graduate students, tech
nicians and many other unnamed colleagues.
P. BOGER, K. HIRAI, AND K. WAKABAYASHI
Konstanz, Germany, Ayase, Kanagawa and Tokyo/Machida, Japan, April 2002
Contents
1 Acetolactate Synthase Inhibitors
TSUTOMU SHIMIZU, ISHIZUE NAKAYAMA, Kozo NAGAYAMA,
TAKESHIGE MIYAZAWA, and YUKIO NEZU
1.1 Introduction ................... ... ........... ....... 1
1.2 Acetolactate Synthase-Inhibiting Herbicides Actively
Developed in the Late 1990s ........ ... .... ... .......... 2
1.3 Discovery of Pyrimidinyl Carboxy Herbicides
(Pyrimidinylsalicylate Class Herbicides) ... ......... ...... 5
1.3.1 Discovery of the Lead Structures. . . . . . . . . . . . . . . . . . . . 5
1.3.2 Discovery and Optimizations of the Secondary
Lead Structure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
1.3.3 Further Optimizations of the Pyrimidinyl
Carboxy Herbicides ........................ ...... 9
1.4 Herbicidal Activity of Pyrimidinyl Carboxy Herbicides ...... 10
1.4.1 Pyrithiobac-Sodium for Use in Cotton ...... ......... 10
1.4.2 Bispyribac-Sodium for Use in Rice .................. 10
1.4.3 Bispyribac-Sodium for Vegetation Management. . . . . . . . 11
1.4.4 Pyriminobac-Methyl for Use in Rice. . . . . . . . . . . . . . . . . 11
1.5 Physiological Plant Response to Pyrimidinyl Carboxy
Herbicides .......................................... 12
1.6 Mode of Action and Selectivity of Pyrimidinyl
Carboxy Herbicides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
1.6.1 Primary Target . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
1.6.2 Inhibition of Bacterial Acetolactate Synthase .... ...... 14
1.6.3 Selectivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
1.7 Biological Characteristics of the Target Enzyme ............ 16
1.7.1 Kinetic Studies of Plant Acetolactate Synthase ......... 16
1.7.2 Subunit Compositions of Plant Acetolactate
Synthase .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
1.7.3 Recombinant Systems. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
1.8 Inhibition Mechanism of the Target Enzyme
by Pyrimidinyl Carboxy Herbicides. . . . . . . . . . . . . . . . . . . . . . . 19
1.8.1 Inhibition Kinetics with Plant Acetolactate Synthase . . . . 19
1.8.2 Inhibition Kinetics with Bacterial Acetolactate
Synthase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
X Contents
1.9 Molecular Genetics of Target Enzyme .................... 22
1.9.1 Acetolactate Synthase Genes of Plants. . . . . . . . . . . . . . . . 22
1.9.2 Acetolactate Synthase-Inhibiting Herbicide-Resistant
Crops (Including Arabidopsis thaliana) and Their
Acetolactate Synthase Genes ....................... 24
1.9.3 Acetolactate Synthase-Inhibiting Herbicide-Resistant
Weeds and Their Acetolactate Synthase Genes ......... 28
1.9.4 Genetic Engineering. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
2 Bleaching Herbicides: Action Mechanism in Carotenoid Biosynthesis,
Structural Requirements and Engineering of Resistance
GERHARD SANDMANN
2.1 Herbicidal Effect and Mode of Action .................... 43
2.2 Interaction of Inhibitors with Carotene Desaturation ........ 44
2.3 Structural Requirements for an Inhibitor
of Phytoene Desaturase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
2.4 Strategies for Genetic Engineering of Herbicide Resistance
by Modification of the Carotenogenic Pathway ............. 50
2.4.1 Overexpression of a Susceptible Lycopene Cyclase
in Synechococcus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
2.4.2 Selection of Mutants with Resistant Phytoene
Desaturase and Gene Transfer into Tobacco. . . . . . . . . . . 51
2.4.3 Naturally Resistant Phytoene Desaturase
from Bacteria and Genetic Engineering
of a Resistant Tobacco. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
2.5 Conclusion and Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
3 Inhibitors of Aromatic Amino Acid Biosynthesis (Glyphosate)
DONALD R. GEIGER and MARK A. FUCHS
3.1 Introduction ........................................ 59
3.2 Symptoms of Herbicidal Activity ........................ 60
3.3 Mode of Action of Glyphosate .......................... 62
3.3.1 Overview of the Mode of Action. . . . . . . . . . . . . . . . . . . . 62
3.3.2 Primary Mode of Action .......................... 64
3.3.2.1 Biochemical Characteristics of the Target
Enzyme................................. 64
3.3.2.2 Structural Characteristics of the Target
Enzyme................................. 65
3.3.2.3 Interaction Between 5-Enolpyruvylshikimate
3-Phosphate Synthase and Glyphosate ......... 66
3.3.2.4 Molecular Requirements for Herbicidal
Activity of Glyphosate . . . . . . . . . . . . . . . . . . . . . . 69
Contents XI
3.3.3 Secondary Physiological Consequences of Inhibition
of 5-Enolpyruvylshikimate 3-Phosphate Synthase ...... 70
3.3.3.1 Inhibition of Chorismate Synthesis. . . . . . . . . . . . 70
3.3.3.2 Depletion of Photosynthetic Carbon
Reduction Cycle Intermediate Metabolites ...... 71
3.3.3.3 Development of Secondary Damage
Symptoms ............................... 72
3.3.3.4 Bases of Development of Lethal Symptoms
Among Species ........................... 72
3.4 Mechanisms for Resistance and Tolerance
to Glyphosate ....................................... 75
3.4.1 Development of Commercially Valuable Glyphosate-
Resistant Plants ................................. 75
3.4.2 Tolerance to Field Doses of Glyphosate
in Field-Grown Plants ............................ 77
3.5 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
References ............................................. 80
4 Inhibitors of Glutamine Synthetase
GUENTER DONN and HELMUT KOCHER
4.1 Introduction ........................................ 87
4.2 Plant Glutamine Synthetase Isoforms and Their Function .... 87
4.3 Glutamine Synthetase Inhibitors ........................ 90
4.4 Discovery of the Herbicidal Activity of Phosphinothricin
and Bialaphos ....................................... 91
4.5 Mode of Glutamine Synthetase Inhibition ................. 92
4.6 Effects of Glutamine Synthetase Inhibitors in Plants . . . . . . . . . 94
4.6.1 Visible Symptoms of Herbicidal Action .............. 94
4.6.2 Physiological Effects of Glutamine Synthetase
Inhibition in Plants by Phosphinothricin ............. 94
4.7 Attempts to Generate Selectivity for Glufosinate ............ 96
4.7.1 Attempts to Select Glufosinate Tolerant Mutants ....... 97
4.7.2 Metabolic Inactivation of Glufosinate by Bar
and Pat Enzymes ................................ 98
References ............................................. 99
5 Acetyl-CoA Carboxylase Inhibitors
MALCOLM D. DEVINE
5.1 Introduction ........................................ 103
5.2 Symptoms of Herbicidal Activity ........................ 103
5.3 Biochemical Characteristics of the Target Enzyme .......... 104
5.4 Mode of Action of Cyclohexanedione
and Aryloxyphenoxypropanoate Herbicides. . . . . . . . . . . . . . . . 105