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University of St. Andrews

1. Zarins-Tutt, Joseph Scott. Gene mining of biosynthesis genes and biosynthetic manipulation of marine bacteria for the production of new antibiotic candidates .

Degree: 2015, University of St. Andrews

Natural product drug discovery has traditionally been the corner stone of medicine having provided cures to many of today’s most common diseases. In particular, antibiotics have revolutionised healthcare and extended human lifespan. However, since their introduction into the clinic, resistance to these drugs has arisen. With the number of new antibiotics being discovered in recent years declining, and fewer drugs making it past clinical trials, we have reached the point where antibiotic resistant infections have become common place and a serious threat to health and society. There is now an urgent requirement for the discovery of new antibiotics and in particular those with unexploited mode of action. This thesis details the different areas of natural product drug development from discovery through to analogue generation. In Chapter one, the history of natural products as therapeutics is explored with a particular focus on antibiotics and how resistance arises against these agents. It outlines why the discovery of new antibiotics is so important and new methods used to facilitate this search. Chapter two follows with the development of a screening platform for antibiotic induction, using the model Streptomyces; Streptomyces coleiolor M145. A variety of culture additives are explored for their ability to induce secondary metabolism production. Chapter three then details the sampling and identification of microbes from a pseudo-marine environment and their screening for their ability to produce secondary metabolites with antibiotic properties. The second half of this thesis centres on the non-ribosomal peptide echinomycin. Collaborators Aquapharm supplied the marine derived strain AQP-4895, capable of producing echinomycin. Chapter four details the establishment of AQP-4895 culturing conditions and the shift observed in production profile. Next Chapter five looks at producing echinomycin analogues through precursor directed biosynthesis. A range of halogenated quinoxaline carboxylic acids are synthesised and fed to AQP-4895, and the respective echinomycin analogues monitored by LC-MS. Chapter Six then aims to direct biosynthesis of the halogenated analogues, using mutasynthesis. Due to the lack of genetic data available surrounding the strain, an unusual approach was taken, using iPCR to create a template for homologous recombination. Advisors/Committee Members: Goss, Rebecca J (advisor).

Subjects/Keywords: Biosynthesis; Antibiotics; Natural products; Actinomycetes; Marine bacteria; iPCR; Echinomycin; Cryptic secondary metabolism

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Zarins-Tutt, J. S. (2015). Gene mining of biosynthesis genes and biosynthetic manipulation of marine bacteria for the production of new antibiotic candidates . (Thesis). University of St. Andrews. Retrieved from http://hdl.handle.net/10023/7690

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Zarins-Tutt, Joseph Scott. “Gene mining of biosynthesis genes and biosynthetic manipulation of marine bacteria for the production of new antibiotic candidates .” 2015. Thesis, University of St. Andrews. Accessed July 03, 2020. http://hdl.handle.net/10023/7690.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Zarins-Tutt, Joseph Scott. “Gene mining of biosynthesis genes and biosynthetic manipulation of marine bacteria for the production of new antibiotic candidates .” 2015. Web. 03 Jul 2020.

Vancouver:

Zarins-Tutt JS. Gene mining of biosynthesis genes and biosynthetic manipulation of marine bacteria for the production of new antibiotic candidates . [Internet] [Thesis]. University of St. Andrews; 2015. [cited 2020 Jul 03]. Available from: http://hdl.handle.net/10023/7690.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Zarins-Tutt JS. Gene mining of biosynthesis genes and biosynthetic manipulation of marine bacteria for the production of new antibiotic candidates . [Thesis]. University of St. Andrews; 2015. Available from: http://hdl.handle.net/10023/7690

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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