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Title: Natural product discovery and biosynthesis from soil actinobacteria
Author: Wang, Xiaoling
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2013
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New structurally diverse natural products can be discovered when carefully designed screening procedures have been applied and when a prolific organism from a different biological source is examined, such as, rare actinobacteria from an untapped environment. Chapter 3 describes the isolation and structure characterisation of eight compounds from the rare actinobacterum, Saccharothrix xinjiangensis (NRRL B-24321), including, two new 16-member macrolides, Tianchimycin A and B, respectively. OSMAC (One Strain - Many Compounds) is used to search bioactive compounds from the metabolic profile of S. xinjiangensis, isolated from a semi-arid or desert area, Tanchi, Xinjiang in the study. Isolated compounds were characterised by NMR spectroscopy and accurate mass spectrometric analysis. Investigations of the natural products at all levels, from genes, to enzymes, to molecules has revealed insights into differentiating features of the biosynthetic pathways that lead to structural diversity of natural products. The presence of a halogen substituent in natural products profoundly influences their biology activity. Actinomycins are a well-known class of antibiotics/anticancer agents. Here, the gene cluster directing chlorinated actinomycin G biosynthesis in Streptomyces iakyrus (DSM 41873) has been identified and sequenced. It contains one actinomycin synthetase I (ACMS I) gene and two copies of ACMS II and III genes. Genetic analysis demonstrates a unique partnership between the putative hydroxylation and chlorination activities as both acm8 and acm9 genes need to be transcribed for the biosynthesis of actinomycin G2 and actinomycin G3, respectively. In chapter 5, I descries a possible metabolic flux rebalancing pathway for increasing phenazinomycin production in S. iakyrus (DSM 41873) after interruption of the methyltrasfer gene (acmG5') in actinomycin G gene cluster. The gene cluster of phenazinomycin was identified by in silico analysis and by comparison with a known phenazine gene cluster from S. iakyrus (DSM 41873).
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Biosynthesis ; Actinobacteria ; Natural products