Electronic Theses and Dissertations

Date of Award


Document Type


Degree Name

Ph.D. in Pharmaceutical Sciences


Biomolecular Sciences

First Advisor

D. Cole Stevens

Second Advisor

Dale G. Nagle

Third Advisor

Vitor H. Pomin


University of Mississippi

Relational Format



Myxobacteria are known for their large genomes that bestow them with a distinct lifestyle that is characterized by fruiting body formation, gliding motility, social interactions, predation, and secondary metabolite production. The powerful combination of whole-genome sequencing and bioinformatics-driven analysis of sequence data has delivered unexpected insights into myxobacterial microbial communities. We applied these two approaches to investigate the chemical space and biosynthetic potential of myxobacteria. Mining different myxobacterial genomes for biosynthetic gene clusters led us to the discovery of a cryptic acyl-homoserine lactone (AHL) synthase encoded in the genome of the myxobacterium Archangium gephyra. Bioinformatic analysis of this AHL synthase using antiSMASH, blastp, MEGA7 HMMSEARCH, and EFI-EST showed that it is highly homologous to other functional bacterial AHL synthases with no cognate AHL receptor encoded in the genome. Heterologous expression of this AHL synthase in Escherichia coli BL21 was performed and it was found to produce detectable quantities of three AHL signals. This is the first example of a functional orphaned LuxI-type AHL synthase reported. This result provides a unique perspective on interspecies cross-talk within polymicrobial communities. We also utilized long-read genomes and modern comparative genomics to investigate the taxonomic rank and biosynthetic potential of four environmental myxobacteria isolated from North American soils and two myxobacteria deposited at the ATCC. Average nucleotide identity and digital DNA–DNA hybridization scores from comparative genomics suggest that the reclassification of Archangium primigenium ATCC 29037 and Chondrococcus macrosporus ATCC 29039 to be potentially novel members of the genera Melittangium and Corallococcus, respectively, and the four isolated myxobacteria to be species from Corallococcus, Pyxidicoccus, and Myxococcus, respectively. In addition, further analysis to assess the biosynthetic potential of these bacteria using high antiSMASH and BiG-SCAPE platforms suggests genus-level conservation of biosynthetic pathways which support our preliminary taxonomic assignments. This result highlights the significance of applying modern genomics to revise myxobacterial taxonomy and improve our understanding of the genetic basis of the social activities and specialized metabolism of myxobacteria.

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