Chromosome architecture as a determinant for biosynthetic diversity in micromonospora

Mark, David R. and Tucker, Nicholas P. and Herron, Paul R. (2024) Chromosome architecture as a determinant for biosynthetic diversity in micromonospora. Microbial Genomics. ISSN 2057-5858 (In Press) (https://doi.org/10.1099/mgen.0.001313)

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Abstract

Natural products – small molecules generated by organisms to facilitate ecological interactions – are of great importance to society, with use as antibacterial, antiviral, antifungal, and anticancer drugs. However, the role and evolution of these molecules and the fitness benefits they provide to their hosts in their natural habitat remains an outstanding question. In bacteria, the genes which encode the biosynthetic proteins that generate these molecules are organised into discrete loci termed biosynthetic gene clusters. In this work, we asked the question, “How are biosynthetic gene clusters organised at the chromosomal level?”. We sought to answer this using publicly available high-quality assemblies of Micromonospora, an actinomycete genus with members responsible for biosynthesising notable natural products such as gentamicin and calicheamicin. By orienting the Micromonospora chromosome around the origin of replication, we demonstrated that Micromonospora have a conserved origin-proximal region, which becomes progressively more disordered towards the antipodes of the origin. We then demonstrated, through genome mining of these organisms, that the conserved origin-proximal region and the origin distal region of Micromonospora have distinct populations of BGCs and in this regard parallel the organisation of Streptomyces with linear chromosomes. Specifically, the origin-proximal region contains highly syntenous, conserved BGCs predicted to biosynthesise terpenes and a type III polyketide synthase. In contrast, the ori-distal region contains a highly diverse population of BGCs, with many BGCs belonging to unique gene-cluster families. These data highlight that genomic plasticity in Micromonospora is locus-specific, highlights the importance of using high-quality genome assemblies for natural product discovery, and helps guide future natural product discovery by highlighting that biosynthetic novelty may be enriched in specific chromosomal neighbourhoods.

ORCID iDs

Mark, David R., Tucker, Nicholas P. ORCID logoORCID: https://orcid.org/0000-0002-6331-3704 and Herron, Paul R. ORCID logoORCID: https://orcid.org/0000-0003-3431-1803;
CORE (COnnecting REpositories)