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Chapter 32 : Pharmacologically Active Agents of Microbial Origin

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Abstract:

Pharmacologically active natural products are generally classified as those useful for treating human diseases and disorders including hyperlipidemia, cancer, immunoregulatory disorders, inflammation, and neurological and metabolic diseases. This chapter reviews the discovery of pharmacologically active microbial metabolites, with an emphasis on recent developments, and considers the specific challenges involved in screening samples derived from microbial fermentations. It discusses high-throughput screening assays used for the discovery of pharmacologically active agents. It also gives specific examples of assays that have resulted in the discovery of new pharmacological agents of microbial origin. The chapter also reviews the selected pharmacologically active agents of microbial origin with utility or potential utility in the areas of immunosuppression, cancer, and cardiovascular and metabolic disease. The microbial products discussed in this chapter range from successful drugs to recently described lead compounds and provide ample testament to the ability of microbial secondary metabolism to provide compounds with real or potential therapeutic utility against a diverse and extensive range of pharmacological targets. The focus of many current microbial product screening operations is returning to antibiotic discovery. It is worth remembering that the discovery route of some very significant pharmacologically active agents of microbial origin has been indirect.

Citation: Wrigley S. 2004. Pharmacologically Active Agents of Microbial Origin, p 356-374. In Bull A (ed), Microbial Diversity and Bioprospecting. ASM Press, Washington, DC. doi: 10.1128/9781555817770.ch32

Key Concept Ranking

Chemicals
0.7104629
Cellular Processes
0.60910827
Programmed Cell Death
0.5453044
Microbial Products
0.53752446
Alkaloids
0.49972612
Carbohydrates
0.47291684
Systemic Lupus Erythematosus
0.45361406
0.7104629
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Figures

Image of Figure 1
Figure 1

Structures of the metabolite L-671,776, (structure 1), the sp. metabolite 9-methoxystrobilurin E (structure 2), the actinomycete metabolite geldanamycin (structure 3), and the fungal metabolite monorden (radicicol) (structure 4).

Citation: Wrigley S. 2004. Pharmacologically Active Agents of Microbial Origin, p 356-374. In Bull A (ed), Microbial Diversity and Bioprospecting. ASM Press, Washington, DC. doi: 10.1128/9781555817770.ch32
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Image of Figure 2
Figure 2

Structures of the immunosuppressants, cyclosporin A (structure 1), from ; FK506 (structure 2) from ; and rapamycin (structure 3) from .

Citation: Wrigley S. 2004. Pharmacologically Active Agents of Microbial Origin, p 356-374. In Bull A (ed), Microbial Diversity and Bioprospecting. ASM Press, Washington, DC. doi: 10.1128/9781555817770.ch32
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Image of Figure 3
Figure 3

Structures of the immunosuppressive lead compounds myriocin A (structure 1) from ; sanglifehrin A (structure 2) from a sp.; XR774 (structure 3) from cf. ; and CJ-14,897 (structure 4) from a sp.

Citation: Wrigley S. 2004. Pharmacologically Active Agents of Microbial Origin, p 356-374. In Bull A (ed), Microbial Diversity and Bioprospecting. ASM Press, Washington, DC. doi: 10.1128/9781555817770.ch32
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Image of Figure 4
Figure 4

Structures of antitumor agents epothilone A (structure 1) from ; fumagillin (structure 2) from ; calicheamicin γ (structure 3) from subsp. ; and XR842 (structure 4) from .

Citation: Wrigley S. 2004. Pharmacologically Active Agents of Microbial Origin, p 356-374. In Bull A (ed), Microbial Diversity and Bioprospecting. ASM Press, Washington, DC. doi: 10.1128/9781555817770.ch32
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Image of Figure 5
Figure 5

Structures of mechanism-based antitumor lead compounds UCN-01 (structure 1) from a Streptomyces sp.; clavaric acid (structure 2) from ; chlorofusin (structure 3) from ; lactacystin (structure 4) from a sp.; and telemostatin (structure 5) from .

Citation: Wrigley S. 2004. Pharmacologically Active Agents of Microbial Origin, p 356-374. In Bull A (ed), Microbial Diversity and Bioprospecting. ASM Press, Washington, DC. doi: 10.1128/9781555817770.ch32
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Image of Figure 6
Figure 6

Structures of the cardiovascular drugs and lead compounds lovastatin (structure 1 ) from ; mevastatin (structure 2) from and ; squalestatin SI from a sp. or zaragozic acid A from an unidentified fungus (structure 3); and pyripyropene A (structure 4) from .

Citation: Wrigley S. 2004. Pharmacologically Active Agents of Microbial Origin, p 356-374. In Bull A (ed), Microbial Diversity and Bioprospecting. ASM Press, Washington, DC. doi: 10.1128/9781555817770.ch32
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Image of Figure 7
Figure 7

Structures of lipstatin (structure 1) from ; acarbose (structure 2) from an sp.; and L-783,281 (structure 3) from a sp.

Citation: Wrigley S. 2004. Pharmacologically Active Agents of Microbial Origin, p 356-374. In Bull A (ed), Microbial Diversity and Bioprospecting. ASM Press, Washington, DC. doi: 10.1128/9781555817770.ch32
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