Analytical microbial natural product chemistry and biosynthe...

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Analytical microbial natural product chemistry and biosynthesis
DTU Department of Systems Biology
General course objectives:
Microorganisms are unique sources for diverse chemistry that can be exploited in biotechnology (e.g. as pharmaceuticals) or feared as contaminants in food or feed (e.g. mycotoxins). The aim of the course is to give the students a fundamental insight into this chemical diversity produced by microorganisms and how they are analyzed. More specifically the course will introduce i) how the various types of natural products are biosynthesized; ii) the different types of unique enzymes that catalyzes their biosynthesis; iii) the nature of the underlying gene clusters; iv) how bioinformatics tools can be used to link genes to chemical structures and vice versa; v) and the analytical methods and strategies to profile, characterize and quantitate such metabolites.
Learning objectives:
A student who has met the objectives of the course will be able to:
  • Define and describe the major classes of natural products (secondary metabolites).
  • Recognize a common polyketide, non-ribosomal peptide or terpenoid type of natural product and predict a likely biosynthetic pathway based on a given structure and retro biosynthetic considerations.
  • To predict the composition of the related biosynthetic gene cluster, based on structural analysis of a given natural product.
  • Require advanced user knowledge of bioinformatic tools, such as antiSMASH, for analysis of secondary metabolite gene clusters.
  • Require advance knowledge of bioinformatics tools such as BLAST, HMMer, Interproscan for prediction of enzyme activities.
  • Require basic knowledge on analysis and handling of microbial whole genome sequence data.
  • Require advanced skills in prediction of types of natural product based on genome analysis.
  • Present one of the major pathways leading to secondary metabolites in some details.
  • Explain the principles of different types of chromatography (RP, HILIC, IC) and pH considerations.
  • Interpret data from mass spectrometry (spectra and chromatograms), isotope and adduct patterns, including interpretation of simple MS/MS spectra and their use in dereplication.
  • Write a report and prepare a scientific presentation within a short timeframe.

Contents:
With onset in microbial metabolites especially fungal, the course will focus on the following topics: a) the biochemistry of the chemodiversity in microorganisms including the biosynthesis of important classes of compounds such as polyketides, terpenoids and alkaloids; b) concept and strategies of metabolite profiling and metabolomics, c) the core analytical methodologies used for detection and analysis of natural products including LC and GC and detectors e.g. UV (diode array detection), fluorescence, evaporative light scattering and especially mass spectrometry (MS), d) data analysis of unit resolution MS and high resolution (TOF) MS atmospheric pressure ionization spectra; e) data interpretation for database searching; f) tentative identification of compounds based on LC-MS data, LogD consideration and ion-exchange sample preparation strategy, and g) Target analysis of known compounds and their metabolites based on LC-MS/MS (triple quadrupole data) including the scan functions of this instrument; h) Solid Phase Extraction (SPE) purification strategies. If possible we encourage and facilitate that the students work on their own data during the course (microbial genome sequence and natural product containing extracts). Please contact us beforehand to arrange this.

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