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Chapter 30 : Screening for Bioactivity

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Abstract:

The present situation in the screening for bioactive compounds is determined by the nearly unlimited capacity in the throughput of assays. The assays include classical antibacterial assays, classical antifungal assays, antitumor assays, enzyme inhibititory assays, antiparasitic assays, herbicidal assays, and algicidal assays. Alexander Fleming was one of the first scientists who used the agar plate diffusion assay to detect antibacterial activity. Most assays are focused on the inhibition of the polysaccharide network of the cell wall of many fungi, which consists of β-1,3-glucan, chitin, and mannan. One of the most promising new antifungals that were detected as glucan synthase inhibitors is the echinocandin lipopeptide group. Antitumor assays for high-throughput screening are mainly based on the specific inhibition of factors belonging to regulatory cascades. Such assays include the inhibition of protein-tyrosin phosphatases, which control the cell cycle or the inhibition of protein-tyrosin kinases. Chemical screening is focused on the chemical diversity produced by microorganisms and on the assumption that each secondary metabolite produced has or had a biological function in the producing organism. Zahner and coworkers modified the method with regard to staining reagents, sample preparation, and variation of culture conditions of the microorganisms, and his group described numerous secondary metabolites having antibacterial, antifungal, antitumor, enzyme inhibitory, or insecticidal activities.

Citation: Fiedler H. 2004. Screening for Bioactivity, p 324-335. In Bull A (ed), Microbial Diversity and Bioprospecting. ASM Press, Washington, DC. doi: 10.1128/9781555817770.ch30

Key Concept Ranking

Antibacterial Agents
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Cyclic Polypeptide Antibiotics
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High-Performance Liquid Chromatography
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Cell Wall Biosynthesis
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Figure 1

Agar plate diffusion assay using as the test organism and agar pieces from actinomycetes cultures. Reprinted from by permission of Springer-Verlag.

Citation: Fiedler H. 2004. Screening for Bioactivity, p 324-335. In Bull A (ed), Microbial Diversity and Bioprospecting. ASM Press, Washington, DC. doi: 10.1128/9781555817770.ch30
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Figure 2

Agar plate diffusion assay using as the test organism. Test solutions are applied on filter disks.

Citation: Fiedler H. 2004. Screening for Bioactivity, p 324-335. In Bull A (ed), Microbial Diversity and Bioprospecting. ASM Press, Washington, DC. doi: 10.1128/9781555817770.ch30
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Figure 3

Structure of rifampin, a semisynthetic therapeutic agent against tuberculosis.

Citation: Fiedler H. 2004. Screening for Bioactivity, p 324-335. In Bull A (ed), Microbial Diversity and Bioprospecting. ASM Press, Washington, DC. doi: 10.1128/9781555817770.ch30
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Figure 4

Thienamycin, a broad-spectrum antibacterial beta-lactam antibiotic produced by .

Citation: Fiedler H. 2004. Screening for Bioactivity, p 324-335. In Bull A (ed), Microbial Diversity and Bioprospecting. ASM Press, Washington, DC. doi: 10.1128/9781555817770.ch30
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Figure 5

Bulging or curling effect caused by inhibitors of the fungal cell wall biosynthesis on the hyphae of ; (a) normal hyphae, (b) abnormal hyphae.

Citation: Fiedler H. 2004. Screening for Bioactivity, p 324-335. In Bull A (ed), Microbial Diversity and Bioprospecting. ASM Press, Washington, DC. doi: 10.1128/9781555817770.ch30
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Figure 6

Structure of bleomycin, an antitumor antibiotic produced by .

Citation: Fiedler H. 2004. Screening for Bioactivity, p 324-335. In Bull A (ed), Microbial Diversity and Bioprospecting. ASM Press, Washington, DC. doi: 10.1128/9781555817770.ch30
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Figure 7

HMG-CoA reductase inhibitors of the compactin type (statins), isolated from various fungi.

Citation: Fiedler H. 2004. Screening for Bioactivity, p 324-335. In Bull A (ed), Microbial Diversity and Bioprospecting. ASM Press, Washington, DC. doi: 10.1128/9781555817770.ch30
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Figure 8

Structures of anthelminthic avermectins produced by .

Citation: Fiedler H. 2004. Screening for Bioactivity, p 324-335. In Bull A (ed), Microbial Diversity and Bioprospecting. ASM Press, Washington, DC. doi: 10.1128/9781555817770.ch30
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Figure 9

Structure of simocyclinones (antibacterial and antitumor antibiotics), inhibitors of gyrase and protein kinase, produced by Tü 6040.

Citation: Fiedler H. 2004. Screening for Bioactivity, p 324-335. In Bull A (ed), Microbial Diversity and Bioprospecting. ASM Press, Washington, DC. doi: 10.1128/9781555817770.ch30
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