The purpose of the thesis is to present the genus Streptomyces, which represents an extremely important source of bioactive compounds, as the majority of all commercially available antibiotics are produced from this genus. Despite the extensive biosynthetic potential, approximately 90% of biosynthetic gene clusters (BGCs) encoding for natural products remain cryptic under standard conditions. Different strategies for the discovery and activation of cryptic biosynthetic gene clusters are presented for the synthesis of novel bioactive compounds. Bioinformatic approaches allow for the prediction of the structure and function of BGCs and the priority with which they are to be experimentally validated. Metabolic engineering replaces regulatory elements and overcomes regulatory hurdles, which increases yield and enables the synthesis of new, previously unknown natural products. In-situ methods allow for the activation of the cryptic biosynthetic pathways in the natural host, whereby examples of the formation of new antibiotics have been achieved. We can conclude that the presented combination of bioinformatics and experimental approaches significantly increases the possibilities of discovering new natural products with potentially important pharmacological properties, which is crucial in combating the growing resistance to antibiotics.
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