Fungi and the Development of Microbiological Chemistry

1.1 Introduction

Fungi are widespread, non-photosynthetic microorganisms that play a vital role in the environment, particularly in the biodegradation of organic material. The study of their metabolites and metabolism has made many contributions to the overall development of chemistry. Although the biosynthetic pathways that fungi utilize to construct their metabolites have general features in common with those found in bacteria, plants and mammals, they differ in detail and the structures of the resultant natural products are often different. This book is restricted to fungal metabolites but the reader should not lose sight of other natural products produced elsewhere in the living world.

Since fungi do not contain chlorophyll and are not photosynthetic organisms, they gain their energy and many of the nutrients to supply their biosynthetic pathways through the degradation of plant and other matter. Their environmental role is that of recycling. Their widespread provenance is often illustrated in one of the first practical exercises of many microbiology courses. A Petri dish containing a nutrient agar is exposed to the atmosphere for a few minutes. It is then incubated to reveal the range of organisms, both bacteria and fungi, whose spores are present in the atmosphere and which fell onto the plate in a relatively short time. It was a chance contaminant of an agar plate that led to the isolation of penicillin and changed the face of medicinal chemistry.

Fungi are eukaryotic organisms with a distinct nucleus, unlike bacteria which are prokaryotes. This also distinguishes them from another wide family of soil microorganisms, the Actinomycetes (e.g. Streptomycetes), which are often considered along with the bacteria. Yeasts, however, are regarded as a unicellular form of a fungus. Some fungi grow in a symbiotic relationship with photosynthetic algae or cyanobacteria in the form of lichens.

Fungi do not grow in isolation. Some attack plants, insects and mammals as pathogens whilst others are saprophytic and grow on dead material. Some live in a positive symbiotic relationship with a host organism. Thus, there are mycorrhizal fungi that are associated with the roots of plants and facilitate the uptake of nutrients by the plant. Others are endophytic organisms that grow within the vascular system of the plant. Throughout the natural world there is a chemical language between the fungus and its host which determines the nature of this relationship. We are beginning to understand the role of fungal and plant metabolites in this ecological communication.

The chemistry of fungi impinges on many aspects of our daily life whether it be in the role of yeasts in the production of bread and wine, the edible mushrooms or the manufacture of antibiotics such as the penicillins. The fungal diseases of crops, ornamental plants and trees and the spoilage of stored foodstuffs are serious economic problems. The control of the phytopathogenic organisms and the detection of their toxic metabolites in the food chain provide further chemical problems.

The microbiological chemist is interested in the structure, chemistry and biological activity of fungal metabolites. The biosynthesis of these metabolites, the sequences, stereochemistry and mechanism of the individual steps, together with the structure and regulation of the enzymes involved, is a major area of enquiry. The ecological chemistry of fungal interactions with plants and insects has provided another area of chemical investigation. An understanding of the chemical basis of fungal bio-control agents may have useful agrochemical applications.

As biodegradative organisms, fungi can carry out microbiological transformations of extraneous chemical substances. They can behave as self-replicating, environmentally friendly, chiral reagents. Their ability to carry out transformations that are chemically difficult, e.g. hydroxylations at sites that are remote from other reactive centres, has been exploited commercially. The scope of these biotransformations and the development of predictive models so that the use of an organism can be built into a synthetic strategy is yet another area of investigation. The use of the biodegradative ability of fungi in the bioremediation of contaminated land is a further application of chemical interest.

There are various estimates of the number of species of fungi. These range from 100 000 to 250 000. What is clear is that only a relatively small number, of the order of a few thousand, have been thoroughly investigated by microbiological chemists. Furthermore, there are often different strains of the same species. Whilst these may be morphologically similar, their metabolites can be quite diverse. Some metabolites may be produced consistently by all the strains of a particular species whilst other metabolites may be variable. The chemistry of an organism can also vary with the conditions under which it is grown. Un-surprisingly, therefore, some species of economic importance, e.g. Penicillium chrysogenum, have generated immense chemical interest.

1.2 Structure of Fungi

At first sight the structures of fungi appear quite diverse. The fruiting body of the common edible mushroom, Agaricus bisporus, is very different from the green Penicillium species growing on the surface of some cheese. However, there are some common features. The basic structural units of most fungi are the filaments known as the hyphae. Collectively, hyphae can aggregate to form a felt known as the mycelium. In some of the higher fungi, the hyphae can aggregate to form long strands and even differentiate to create a structure almost like a boot-lace, which is known as a rhizomorph. Another name for the honey-fungus, Armillaria mellea, which does considerable damage to trees, is the 'boot-lace fungus', which aptly describes the rhizomorphs by which it spreads underground.

The higher fungi, the mushrooms and toadstools, develop complex and readily observable structures known as fruiting bodies. These sprout from their mycelium, particularly in the autumn, and produce spores. At the other extreme some unicellular micro-fungi, such as the yeasts, produce small globular or ellipsoid cells that are only visible under the microscope.

The hyphae may be long single multi-nucleate aseptate (undivided) cells through which the cellular cytoplasmic fluids may flow. Other hyphae are septate and have distinct divisions. In these much of the chemical activity takes place at the growing tip. The lower micro-fungi only become septate as the culture ages whilst the higher macro-fungi become septate at an early stage and, as rhizomorphs are formed, their function may differentiate.

The...