Date of Award

Spring 2019

Project Type

Thesis

Program or Major

Genetics

Degree Name

Master of Science

First Advisor

Brian M Barth

Second Advisor

Krisztina Varga

Third Advisor

Colin McGill

Abstract

Biotransformation is the use of an organism’s metabolic system to process compounds of interest and induce chemical modifications. Natural products, including those that have antitumor properties, can be biotransformed in an effort to increase the potency of the synthesized bioactive chemicals. This study investigated the potential of a bacterial isolate of the Streptomyces genus to biotransform ursolic acid (UA). Ursolic acid (UA) is an antileukemic compound derived from the ethnobotanical Northern Labrador Tea. Streptomyces derived natural products have been developed into chemotherapeutics including Daunorubicin and Doxorubicin, among others. The collection, isolation, purification, sequencing, and identification of a Streptomyces species from a bear fecal sample, referred to as Streptomyces akac8, was successful. The biotransformation of UA did not yield. A bioinformatics approach was taken to investigate the diversity and phylogenetic distribution of biosynthetic gene clusters (BGCs) harbored in 1,110 Streptomyces genomes. A prioritization of the most prolific natural product producer strains was established and a strain specific analysis identified possible naturally occurring analogs of 38 existing chemotherapeutic gene clusters (CGCs). This was one of the largest BGC study of a single genus to date. Our results indicate a wide phylogenetic spread of CGCs beyond the established species associated with the production of specific chemotherapeutics. We also found diverse BGC content in closely related strains. Finally, based upon our findings of variably distributed constituents of BGCs within the Streptomyces genus we promote the use of population-level drug discovery efforts.

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