Secondary Metabolites

The families of low molecular weight compounds that have no obvious role in the life cycle of producing species, often produced after active growth has ceased, are called secondary metabolites. Both biologically and chemically, secondary metabolites are extremely diverse; however, they arise from just a few biosynthetic pathways based in primary metabolism. Acetate-derived polyketides and amino acid-derived compounds are the most important biosyn-thetic routes in filamentous fungi, including aspergilli. Members of the genus Aspergillus are prolific producers of these natural products, and the structures of a large number of secondary metabolites from Aspergillus have been elucidated by chemists (19,20).

In general, the most famous natural products are bioac-tive and are classified on the basis of this activity as antibiotics, chemotherapeutic agents, toxins, and so forth (21). The single best-known fungal secondary metabolite is the antibiotic penicillin. Although several species of Aspergillus make penicillin, and although A. nidulans has been developed as a model system for studying its biosynthesis, high-yielding industrial fermentations all use strains of Penicillium.

Economically speaking, toxic secondary metabolites of Aspergillus are more important than the medically useful ones. Aflatoxins and sterigmatocystins, for example, cause millions of dollars of damage in agriculture each year (see "Mycotoxins"). Currently, the most important pharmacological agent is lovastatin (mevinolin) a potent inhibitor of cholesterol synthesis, derived from Aspergillus terreus. Lo-vastatin is a polyketide. Several amino acid-derived metabolites also show pharmacological activity. For example, echinocandin B (cilofungin), produced by A. nidulans and Aspergillus rugulovalvus (also called E. rugulosis), is under development as an antifungal agent (Table 2).

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