Metabolomics and Dereplication Strategies in Natural Products
互联网
377
Metabolomic methods can be utilized to screen diverse biological sources of potentially novel and sustainable sources of antibiotics and pharmacologically-active drugs. Dereplication studies by high resolution Fourier transform mass spectrometry coupled to liquid chromatography (LC-HRFTMS) and nuclear magnetic resonance (NMR) spectroscopy can establish the chemical profile of endophytic and/or endozoic microbial extracts and their plant or animal sources. Identifying the compounds of interest at an early stage will aid in the isolation of the bioactive components. Therefore metabolite profiling is important for functional genomics and in the search for new pharmacologically active compounds. Using the tools of metabolomics through the employment of LC-HRFTMS as well as high resolution NMR will be a very efficient approach. Metabolomic profiling has found its application in screening extracts of macroorganisms as well as in the isolation and cultivation of suspected microbial producers of bioactive natural products.
Metabolomics is being applied to identify and biotechnologically optimize the production of pharmacologically active secondary metabolites. The links between metabolome evolution during optimization and processing factors can be identified through metabolomics. Information obtained from a metabolomics dataset can efficiently establish cultivation and production processes at a small scale which will be finally scaled up to a fermenter system, while maintaining or enhancing synthesis of the desired compounds. MZmine (BMC Bioinformatics 11:395–399, 2010; http://mzmine.sourceforge.net/download.shtml ) and SIEVE (http://www.vastscientific.com/resources/index.html ; Rapid Commun Mass Spectrom 22:1912–1918, 2008) softwares are utilized to perform differential analysis of sample populations to find significant expressed features of complex biomarkers between parameter variables. Metabolomes are identified with the aid of existing high resolution MS and NMR records from online or in -house databases like AntiMarin, a merger database of Antibase (Laatsch H. Antibase Version 4.0 – The Natural Compound Identifier. Wiley-VCH Verlag GmbH & Co. KGaA, 2012) for microbial secondary metabolites as well as higher fungi and MarinLit for marine natural products (Blunt J. MarinLit. University of Canterbury, New Zealand, 2012). This is further validated through available reference standards and NMR experiments. Metabolomics has become a powerful tool in systems biology which allows us to gain insights into the potential of natural isolates for synthesis of significant quantities of promising new agents and allows us to manipulate the environment within fermentation systems in a rational manner to select a desired metabolome.
