Abstract
Despite the fact that natural products have historically been a prolific source of new compounds, pharmaceutical drug discovery programs have moved away from natural products in favor of synthetic approaches. However, the abundance of synthetic compounds with similar functional groups and, therefore, limited chemical diversity has renewed interest in nature as a good resource for finding new ideas to be applied to the design of the next generation of drugs. One of the main issues for drug discovery programs based on microbial natural products is how to obtain the maximum potential from microbial strains in terms of chemical diversity of the metabolites produced. Several approaches are now available for enhancing the production and diversity of secondary metabolites from wild-type microorganisms. Automated comparisons of the metabolite profiles of microorganisms can be used as a valuable method for building libraries of natural products for drug discovery. Specific computer analyses of high-performance liquid chromatography chromatograms from organic extracts of fermented microorganisms can be used as a tool for increasing chemical diversity of collections, media improvement, evaluation of natural products libraries, and even determination of taxonomic correlations. Examples of what can be done using some of the new generation of software tools to compare profiles of secondary metabolites include the evaluation of extraction solvents and fermentation formats for the design of natural-product collections, and even the determination of relationships among strains from different origins.
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References
Oprea TI, Davis AM, Teague SJ, Leeson P. Is there a difference between leads and drugs? A historical perspective. J Chem Inf Comput Sci 2001;41:1308–1315.
Lipinski CA, Lombardo F, Dominy BW, Freeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 1997;23:3–25.
Peláez F, Genilloud O. Microorganisms for Health Care, Food and Enzyme Production. 1. Discovering new drugs from microbial natural products. Research Signpost Ed, Kerala, India. 2003;1–22.
Müller-Kuhrt L. Putting nature back into drug discovery. Nature Biotech 2003;21:602.
Bindseil KU, Jakupovic J, Wolf D, Lavayre J, Leboul J, van der Pyl D. Pure compound libraries; a new perspective for natural product based drug discovery. Drug Disc Today 2001;6:840–847
Yarbrough GG, Taylor DP, Rowlands RT, Crawford MS, Lasure L. Screening microbial metabolites for new drugs: theoretical and practical issues. J Antibiot 1993;46:535–544.
Cordell GA, Shin YG. Finding the needle in the haystack. The dereplication of natural product extracts. Pure Appli Chem 1999;71:1089–1094.
Monaghan RL, Polishook JD, Pecore VJ, Bills GF, Nallin-Omstead M, Streicher SL. Discovery of novel secondary metabolites from fungi—is it really a random walk through a random forest? Can J Bot 1995;73:S925–S931.
García JB, Tormo JR. HPLC Studio: a new software utility to perform HPLC chromatogram comparison for screening purposes. J Biomol Screen 2003;8:305–315.
Tormo JR, García JB, DeAntonio M, et al. A method for the selection of production media for actinomycete strains based on their metabolite HPLC profiles. J Ind Mic Biotech 2003;30:582–588.
Platas G, Collado J, Martínez H, Arrese M, Peláez F, Díez MT. Implementation of conditions of the inoculum stage for Streptrosporangium cultures. Microbiologia SEM 1997;13:193–200.
Platas G, Peláez F, Collado J, Martinez H, Diez MT. Nutritional preferences of a group of Streptosporangium soil isolates. J Biosci Bioen 1999;88:269–275.
Hewlett Packard, Agilent. 1995. Understanding Your ChemStation, 5th ed. San Diego, CA, USA.
Julian RK, Jr, Higgs RE, Gygi JD, Hilton MD. A method for quantitively differentiating crude natural extracts using high-performing liquid chromatography-electrospray mass spectrometry. Anal Chem 1998;70:3249–3254.
Schmid I, Sattler I, Grabley S, Thiericke R. Natural products in high throughput screening: automated high-quality sample preparation. J Biomol Screen 1999;4:15–25
Stackebrandt E, Rainey FA, Ward-Rainey NL. Proposal for new hierarchic classification system, Actinobacteria classis nov. Int J Syst Bacteriol 1997;47: 479–491.
Vilella D, Sánchez M, Platas G, et al. Inhibitors of farnesylation of Ras from a microbial natural products screening program. J Ind Mic Biotech 2000;25:315–327
Vandamme P, Pot B, Gillis M, de Vos P, Kersters K, Swings J. Polyphasic taxonomy, a consensus approach to Bacterial Systematics. Microbiol Rev 1996;60:407–438.
Fiedler HP. Biosynthetic capacities of actinomycetes. 1. Screening for secondary metabolites by HPLC and UV-visible absorbance spectral libraries. Nat Prod Lett 1993;2:119–128.
Sneath PH, Sokal RR. Taxonomic structure. In: Numerical Taxonomy (Kennedy D and Park RB, ed), WH Freeman & Co., San Francisco, USA, 1973, pp. 230–234.
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© 2005 Humana Press Inc., Totowa, NJ
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Tormo, J.R., García, J.B. (2005). Automated Analyses of HPLC Profiles of Microbial Extracts. In: Zhang, L., Demain, A.L. (eds) Natural Products. Humana Press. https://doi.org/10.1007/978-1-59259-976-9_3
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DOI: https://doi.org/10.1007/978-1-59259-976-9_3
Publisher Name: Humana Press
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