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132 CHAPTER 7

difference between fungi and other organisms indicates

a clear, and ancient, evolutionary divergence.

Secondary metabolism

The term secondary metabolism refers to a wide

range of metabolic reactions whose products are not

directly or obviously involved in normal growth. In this

respect, secondary metabolism differs from intermedi-

ary metabolism (the normal metabolic pathways dis-

cussed earlier in this chapter). Thousands of secondary

metabolites have been described from fungi (Turner

1971; Turner & Aldridge 1983), and the only features

that they have in common are:

• they tend to be produced at the end of the expon-
  ential growth phase in batch culture or when
  growth is substrate-limited in continuous culture
  (Chapter 4);


• they are produced from common metabolic inter-
  mediates but by special enzymatic pathways
  encoded by specific genes;


• they are not essential for growth or normal
  metabolism;


• their production tends to be genus-, species- or even
  strain-specific.

Interest in this diverse range of compounds stems
mainly from their commercial or environmental signi-
ficance. For example, the penicillins(from Penicillium
chrysogenum), the structurally similar cephalosporins
(from Cephalosporium or Acremonium species), and
griseofulvin (from P. griseofulvum) are antibiotics
produced commercially from fungi. The darkly
pigmented melanins in some fungal walls are also sec-
ondary metabolites, as are the carotenoid pigmentsin
the conidia of fungi such as Neurospora crassa. These
compounds help to protect cells from damage caused

by reactive oxygen species, such as hydrogen peroxide

and superoxide (Chapter 8). Some secondary meta-

bolites are plant hormones, such as the gibberellins

used commercially in horticulture. The initial discovery

of gibberellins was made during studies of a plant disease

• the bakanae disease of rice, caused by the fungus
  Gibberella fujikuroi. In this disease the shoots elongate
  markedly owing to the production of gibberellins by
  the parasitic fungus. Some secondary metabolites are
  involved in differentiation, examples being the fungal
  sex hormones discussed in Chapter 5. Others are mar-
  keted as pharmaceuticals, including ciclosporin A
  which suppresses organ rejection in transplant surgery.
  Further examples include the mycotoxins, such as the
  aflatoxinsproduced by Aspergillus flavusand A. para-
  siticus(Fig. 7.19) and the ergot alkaloidsproduced by
  Claviceps purpurea(Fig. 7.18) and related species.
  This list of examples could go on, but many secondary
  metabolites have no obvious role in the life of the
  producer organism, and mutated strains that do not
  produce these compounds often grow as well as the
  wild-type strains in culture. This raises the question of
  why secondary metabolites are produced in such
  diversity and abundance, especially since they are
  encoded by cassettes of genes that could be expected
  to be lost if they confer no selective advantage.
  One plausible suggestion is that the process of
  secondary metabolism is necessary, regardless of
  the end products. According to this view, secondary
  metabolism acts as an overspill or escape valve, to
  remove intermediates from the basic metabolic path-
  ways when growth is temporarily restricted. This is
  similar to the explanation we noted earlier for the
  overproduction of organic acids: an organism needs to
  maintain the basic metabolic pathways during periods
  when growth is restricted, but the common metabolic
  intermediates cannot be allowed to accumulate
  because they would disrupt normal metabolism. So, it

Fig. 7.12Structure of the amino acid lysine, and

the characteristic intermediates of the two distinct

lysine biosynthesis pathways.