Microbial products screening

Nisbet, L.J. and Westley, J.W. (1986) Developments in microbial products screening. In Bristol, J.A. (ed.). Annual Reports in Medicinal Chemistry, pp. 149-157. Academic Press, San Diego. 

Here again I should like to backtrack to 1951. At that time resistcuit orgcuiisms except for streptomycin-resistant tubercle bacilli had not yet appeared and the chemotherapy of bacterial diseases seemed to be almost completed. Therefore, I endeavored to extend antibiotic research to a new area and initiated the screening of antitumor antibiotics. I reported the discovery of two microbial products, svibstance No. 289 and sarkonycin (67). 

Screening of microbial products has led to the discovery of a number of growth-inhibiting compounds that have proved to be clinically useful in cancer chemotherapy. Many of these antibiotics bind to DNA through intercalation between specific bases and block the synthesis of RNA, DNA, or both cause DNA strand scission and interfere with cell replication. All of the anticancer antibiotics now being used in clinical practice are products of various strains of the soil microbe Streptomyces. These include the anthracyclines, bleomycin, and mitomycin. 

In 1989, an experimental study designed by the International Dairy Federation in 53 laboratories of 22 different countries to achieve deeper insight into state of proficiency of routinely applied tests showed that the most frequently used microbial inhibitor screening tests were the disc assays with Bacillus stearo-tliermopliilus, Delvotest-P, Brilliant black reduction test, acidification test, CHARM II test, and the Penzyme test (32), Currently available microbial inhibitor tests for screening of residual antibacterials in milk and milk products are presented in Table 27.1. 

Traditional approaches for natural product screening in drug discovery involve the testing of crude extracts obtained from microbial fermentation broths, plants, or marine organisms. When activity above a certain level is detected, active components are isolated and purified for identification. This process is often time consuming where the physicochemical characteristics of the active components are determined, known compounds are identified (dereplication), and the novel compounds are scaled-up for more detailed investigation. 

From this screening work, it is expected that novel microbial products which affect the ACAT-1, TG synthetic pathway or unknown sites responsible for macrophage-derived foam cell formation will be discovered, leading to a new type of anti-atherosclerotic agent and providing a novel target for pharmaceutical intervention. 

H Umezawa (1980) Screening of small molecular microbial products modulating immune responses and bestatin, Recent Results Cancer Res 75 115-125... 

This chapter describes the discovery of micafungin, which was the result of screening for novel antifungals from microbial products.17 We believe that this discovery is not simply a fortuitous event, but rather the fruit of long-term efforts and enthusiasm fuelled by the initial discovery of pyrrolnitrin. 

Microbial Sources. In many cases, screening for the microbial production of volatiles can be achieved by selecting pure cultures of microorganisms from public collections such as the American Type Culture Collection (ATCC). The chances of obtaining an effective culture can often be improved by selecting organisms known to perform the desired types of reactions. 

Zahner, H., Drautz, H., Weber, W. Novel approaches to metabolite screening. In Bioactive Microbial Products Search and Discovery (Bu Lock, J. D., Nisbet, L. J., Winstanley, D. J., Eds). Academic Rress London, 1982, pp. 51-70. 

Fiedler, H. P. (1984) Screening for new microbial products by HPLC using a photodiode array detector. J. Chromatogr. 316,487-494... 

The Microbial Product Library for high-throughput screening at Lepetit Research Center ... 

The Microbial Strain Collection and the Microbial Product Library are currently used in our internal process for the discovery of novel antiinfective agents and for the structural manipulation of proprietary lead compounds through our technologies in biotransformation. Our asset in strain isolation, natural product chemistry and manipulation of lead structures together with our capacity in HTS can also be provided to interested partners in joined research programs for the screening/improvements of biocatalysts. 

Figure Integrated scheme for natural product screening for the example of pharmacologically active microbial secondary metabolites.

The cost of microbial production of chitinous compounds is an important factor in evaluation of their suitability for industrial application. Intensive efforts have been made to optimize the fermentation process for the production of chitin/chitosan with a view to develop economically feasible technologies. The research has been focused on several major aspects improvement of the yields of chitin/chitosan by screening new microbial sources, and optimization of the fermentation conditions and extraction procedures. An understanding of the structure/function relationships of the... 

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