Comparative genomics to understand specialised metabolism in Micromonospora

Student thesis: Doctoral Thesis

Abstract

Hyphal, sporulating members of the Actinomycetota (actinomycetes) – genera such as Micromonospora and Streptomyces – are notable for production of multiple useful antibiotic natural products. The aim of this project was to screen actinomycete isolates from the Atacama Desert and Scottish soil for production of natural product antibiotics which inhibit the growth of Pseudomonas aeruginosa, a frequently multidrug resistant pathogen, and to sequence the genomes of producing organisms to identify biosynthetic gene clusters (BGCs) which drove that activity. Here we report the sequence of four actinomycetes – one Streptomyces isolate from Glasgow Botanic Gardens (S. sp. GBG 9AT) and three Micromonospora (Micromonospora sp. O3, Micromonospora sp. O5, and Micromonospora sp. PH63) isolated from Atacama Desert Soil. Multiple Sequence Alignment based phylogeny and average nucleotide identity (ANI) calculations identified S. sp. GBG 9AT as Streptomyces xanthophaeus, a well characterized streptomycete. The same methodology identified the three Micromonospora isolates as three novel genospecies. All organisms were BGC rich. We also sought out to examine possible regulation of these BGCs. Of well-known developmental regulators conserved within Streptomyces, we identify the master regulator BldD as the only universally conserved regulator within the three Micromonospora. In addition, the three strains are predicted to lack functional BldA, a developmentally regulated tRNA which controls morphological differentiation and antibiotic production. Finally, we analysed the loci of BGCs in single contig assemblies of Micromonospora and identify two distinct populations of BGCs occupying the oriCproximal and oriC-distal regions of the chromosome, a distribution distinct from that of Streptomyces. This work shows a genomic landscape in Micromonospora which is distinct from that of previously studied actinomycetes and lays the groundwork for future studies of the evolution of antibiotic production in these organisms.
Date of Award23 Sept 2023
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SponsorsUniversity of Strathclyde
SupervisorPaul Herron (Supervisor) & Nicholas Tucker (Supervisor)

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