Date of Submission
Campus Only Senior Thesis
Bachelor of Arts
Ethan Van Arnam
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.
Tran, Janet, "Genomic Analysis of the Novel Antibiotic Nocamycin O" (2021). CMC Senior Theses. 2530.
This thesis is restricted to the Claremont Colleges current faculty, students, and staff.