Graduation Year

2021

Date of Submission

11-2020

Document Type

Campus Only Senior Thesis

Degree Name

Bachelor of Arts

Department

Chemistry

Reader 1

Ethan Van Arnam

Reader 2

Aaron Leconte

Abstract

Natural products derived from symbiotic relationships are a promising source of new antibiotics. Fungus-growing ants and actinobacteria are in a mutualistic symbiosis where antibacterial compounds produced by the actinobacteria living on the ant help fight off pathogenic bacteria from its cultivar fungus. A strain of actinobacteria, Amycolatopsis, has been identified on the fungus-growing ant Trachymyrmex smithi and shown to produce a potentially new compound with antibacterial and antifungal properties, now known as nocamycin O. To better understand the new Amycolatopsis strain, 17SM-2A, its genome was sequenced and compared to other genomes for homologous genes that could allude to their function. Similar compounds to nocamycin O, determined by an analysis of a biosynthetic gene cluster in 17SM2A, are nocamycin I, streptolydigin, and tirandamycin. The similarity of these clusters to that of nocamycin O is consistent with the similarity in their chemical structures. All three compounds are thought to inhibit RNA polymerase in some form, which strongly suggests that nocamycin O also functions as an RNA polymerase inhibitor. Of these clusters, the nocamycin I cluster had the highest percentage of similar genes at 72%, but differences between them suggest that nocamycin O is a novel member of the nocamycin family. An analysis of cytochrome P450 genes, which are enzymes that oxidize a substrate, in the clusters revealed that nocamycin O has an extra cytochrome P450 gene, which is consistent with the fact that nocamycin O has an extra oxygen compared to nocamycin I. The presence of a similar cluster to nocamycin O, as seen in the Amycolatopsis keratiniphila genome, suggests that other bacteria in addition to 17SM-2A have the ability to produce nocamycin O. Protein sequence analysis of the RNA polymerase subunit did not confirm that 17SM-2A has self-resistance mechanisms similar to that of the streptolydigin producing Streptomyces lydicus, but there are potential residues that may impart 5 self-resistance. These findings point to nocamycin O being a novel compound with potential as an antibiotic.

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