Table Of ContentA Specialist Periodical Report
B iosynthesis
Volume 1
A Review of the Literature Published
during 1970 and 1971
Senior Reporter
T. A Geissman, Department of Chemistry, University of
California at Los Angeles, U.S.A.
Reporters
S. A Brown, Trent University, Peterborough, Ont., Canada
T. W. Goodwin, University of Liverpool
J. R. Hanson, University of Sussex
J. B. Harborne, University of Reading
E. Leete. University of Minnesota, Minneapolis, U.S.A.
H. H. Rees, University of Liverpool
@ Copyright 1972
The Chemical Society
Burlington House, London, WIV OBN
ISBN: 0 85186 503 8
Library of Congress Catalog Card No. 72-83455
Set in Monophoto Times and printed in England
by Page Bros (Norwich) Ltd. Norwich
Introduction
This is the first volume of a series of Specialist Periodical Reports dealing with
the synthesis of organic compounds in living organisms. Progress in the study
of the biosynthesis of naturally occurring compounds during the past half-
century has been steady, and occasional dramatic leaps have allowed rapid
acceleration along several avenues of the study. Recognition of the funda-
mental progenitors acetyl coenzyme A, the isopentenyl pyrophosphates, and
shikimic acid has made possible the development of those rational conjectures
that have formed and continue to form the basis for experimental verification.
There are few naturally occurring compounds, the origins of whose constituent
parts cannot now be envisaged and for which rational biosynthetic pathways of
high probability cannot be put forward. The testing of such hypotheses by
experiments in living plants and in isolated tissue systems with the aid of
isotopically labelled compounds can now be regarded as classical.
Biosynthetic experimentation with the aim of establishing the origin of a
natural substance in terms of its skeletal structure and the manner in which the
simple precursors are combined stilkeontinues, for that which often appears
obvious deserves, and sometimes demands, final proof. But biosynthetic
inquiry is finding new directions and is now seeking answers to more elusive
questions. Greater emphasis is being directed to the separate and individual
stages through which precursors are altered by bond-forming processes,
rearrangements, oxidations. reductions, etc. Stereochemistry, which has long
played a central role in considerations of biosynthesis, is becoming increasingly
used in studies in which the intricate details of biochemical processes are being
revealed by the use of selected stereomers and by chiral replacement of hydrogen
with its isotopes. A developing area, still in its infant stage, will in time see the
detailed description of synthetic sequences as specific enzymatically catalyzed
processes, each step of which can be understood as a discrete reaction.
In this Volume the contributors have reviewed progress made during 1970
and 1971, with such references to earlier work as are necessary to the context.
An introductory chapter on the methodology of biosynthetic experimentation
provides a general background to the specific topics discussed in the following
sections.
It will be noted that what are perhaps the two most active areas of bio-
synthetic study- alkaloids and terpenoid compounds- are included in other
Specialist Periodical Reports titles. Thus, in their treatment here less emphasis
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has been ghen to such matters as structure determination and the identification
of principal pathways and precursors, and more to such biochemical details
as are known describing natural synthetic processes at the cellular level.
The organization of the subject into sections based upon compound types
makes it impossible to avoid overlap in the treatment of some substances,
the structures of which may place them under one rubric, their biosynthetic
affinities under another. Certain biosynthetic processes common to the
natural formation of compounds of all kinds. including the introduction of
methq 1. methylenedioxy, acyl and glycosyl groupings, are not treated separately
here. They will be seen to be constituent processes in the formation of the
principal classes of most natural substances. which are dealt with under
generally accepted categories.
T. A. GEISSMAN
Con tents
Chapter 1 Methodology
By S. A. Brown
1 Introduction 1
2 Some General Considerations
Definition of Bio synt h esis
Approaches to the Study of Biosynthesis
Limitations on Biosynthetic Studies
3 Sequential Analysis 4
4 Isotopic Tracer Methods 6
The Time and the Place 7
Direct Comparison of Labelled Compounds as Precursors 9
Criteria for Assessment of Precursor Effectiveness 9
Dilution Value and Per Cent Incorporation 9
Extent of Label Randomization 13
Double and Multiple Labelling 17
Trapping and Isotope Competition 23
Kinetic Experiments 26
5 Methods Employing Mutants 29
6 Use of Specific Enzyme Inhibitors 32
7 Administration of Substrates 33
Gaseous Substrates 33
Substrates in Solution 34
Problems of Solubility 34
Administration to Animals 36
Administration to Plants 37
Administration to Microbial and Other Cell Cultures 39
Chapter 2 Biosynthesis of Terpenoid Compounds :
C-C, ,, Compounds
By J. R. Hanson
1 Introduction 41
Contents
2 Mevalonic Acid 41
3 Hemiterpenoids 43
4 Monoterpenoid Compounds 45
5 Iridoids 48
6 Sesquiterpenoid Compounds 52
7 Diterpenoid Compounds 54
Chapter 3 Biosynthesis of Triterpenes, Steroids, and Carotenoids
By H. H. Rees and T. W. Goodwin
1 Introduction 59
2 Squalene 59
3 Formation and Cyclization of Squalene 2,SOxide 68
4 Steroids in Vertebrates 75
Cholesterol Biosyn t hzsis 75
Reduction of the AL'-Bond 75
Demethylation at C(4) and C(14) 76
Transposition of the A*-Bond to the AS-Position 81
General Aspccts of Cholcsterol Biosynthesis 83
Further Metabolism of Cholesterol 84
Steroid Hormones 84
Bile Acids 90
5 Triterpenes and Steroids in Higher Plants, Algae, and
Fungi 93
Phytosterol Biosynthesis 93
Overall Pathway 93
24-Alkylation and Introduction of a A22-Bond 97
General Aspects of Phytosterol Biosynthesis 98
Further Metabolism of Plant Sterols 99
6 Triterpenes and Steroids in Invertebrates 100
Sterol Biosynthesis 100
Metabolism of Stcrols 104
Insects 104
Invertebrates other than Insects 107
7 Carotenoids 108
Introduction 108
Phytoene Formation 108
Conversion of Phytoene into Lycopene 1a 9
Cyclization of Lycopene 112
Other Reactions of Lycopene 114
Insertion of Oxygen 117
Torularhoding Biosynthesis 118
Photoinduction of Carotenogenesis in Non-photo-
synthetic Bacteria and Fungi 118
Contents
Chapter 4 Biosynthesis of Phenolic Compounds
By J. B. Harborne
1 Introduction 119
2 Phenols and Phenolic Acids 120
Salicylic Acid and its 6-Methyl Derivative 120
Biosynthesis of Asperugin 121
Biosynthesis of Mycophenolic Acid 122
Tropolones 123
The NIH Shift and the Synthesis of Simple Phenols 123
3 Phenylpropanoid Compounds 124
Biosynthesis of Cinnamic Acids 124
Allylphenols 125
Biosynthesis of Coumarin 126
Biosynthesis of Scopoletin 127
The Glucosylation of Hydroxycoumarins 128
Furanocoumarins 129
Biosynthesis of Lignins 131
4 Flavonoids 132
The Main Pathway 132
Enzymology of Flavone Synthesis 133
Phenylanaline Ammonia Lyase (PAL) 137
Is PAL an Obligatory Enzyme for Flavonoid
Synthesis ? 139
Phenolases and Peroxidases in Phenolic Synthesis 14 1
Oxidation of Tea Catechin 143
Turnover of Flavonoids 144
Anthocyanin Synthesis 144
Biogenetic-type Syntheses 145
5 Isoflavonoids 146
Biosynthesis of Coumestrol 146
Rotenoid Biosynthesis 147
O-Methylation of Isoflavones 149
6 Xanthones and Stilbenes 150
Xanthones and Benzophenones 150
Stilbenes 151
7 Quinones 153
Benzoquinones 153
Naph thoquinones 154
Anthraquinones 155
Perinaphthenones 157
Chapter 5 Biosynthesis of Alkaloids
By E. Leete
1 Introduction 158
Contents
2 Indole Alkaloids 160
3 The Role of Glycine in the Biosynthesis of the Terpene
Moiety of the Indole and Related Alkaloids 161
4 Aporphine Alkaloids 170
5 Stereochemistry of Hydroxylations involved in Alkaloid
Formation 171
6 Enzyme Studies 173
Lophophora williamsii 173
Vinca rosea 173
Conium rnacrilatiirn 176
Other Enzyme Studies 177
Author index 24 1
