A quantitative study of the relationships between morphology, physiology and geldanamycin synthesis in submerged cultures of Streptomyces hygroscopicus var. geldanus
Dobson, Lynne (2008) A quantitative study of the relationships between morphology, physiology and geldanamycin synthesis in submerged cultures of Streptomyces hygroscopicus var. geldanus. PhD thesis, Dublin City University.
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Microbially produced secondary metabolites such as antibiotics have tremendous economic importance. However, most are produced by filamentous organisms which exhibit diverse growth patterns presenting challenges for industrial fermentation. There are many factors affecting secondary metabolite production which concomitantly impact on morphology, thus it is difficult to distinguish the key driver for productivity. Streptomyces spp. is a genus of filamentous organisms that together synthesise over 4000 bioactive compounds. Streptomyces hygroscopicus var. geldanus produces the secondary metabolite geldanamycin, a novel chemotherapeutic compound, in submerged fermentation. This organism represents an ideal system for experimentation in order to elucidate the relationships between morphology, physiology and secondary metabolite production.
The effects of a variety of microbiological (inoculum size), physical (glass beads) and chemical (surfactants, calcium ions, magnesium ions) factors on morphological development were examined as part of this study. Inclusion of the divalent cations magnesium or calcium was demonstrated to alter the cell surface hydrophobicity of the organism, provoking dispersion or aggregation of cells respectively, and stimulating great disparity in geldanamycin yields. Indeed, in all instances, morphology was found to impact considerably on secondary metabolite formation, with smaller pellet sizes optimal for geldanamycin synthesis. Investigation of the respiration rate of Streptomyces hygroscopicus var. geldanus revealed that a linear relationship existed between this parameter and geldanamycin production. Submerged cultures consisting primarily of small pellets, less than 0.5mm in diameter, were more metabolically active and concomitantly produced more geldanamycin. Nonetheless, it was also demonstrated that other explicit factors exist which do not affect morphology or respiration but regulate geldanamycin synthesis through feedback inhibition of the direct metabolic pathway.
This study has demonstrated that, in Streptomyces hygroscopicus var. geldanus, the bulk of factors that affect morphology impact significantly on respiration, and it is this parameter that is the key driver of secondary metabolite production. This case study provides new insights into the regulation of geldanamycin production in Streptomyces hygroscopicus var. geldanus and provides a basis for elucidation of the relationships between morphology, physiology and secondary metabolism in other filamentous micro-organisms.
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