Gomez-Escribano, J. P. | bioRxiv Science

bioRxiv2026

Genome evolution during the domestication of an antibiotic-producing Streptomyces strain

The domestication of Streptomyces species for antibiotic production involves long-term, iterative mutagenesis and selection, yet the genomic changes driving enhanced production remain unclear. Analysis of five strains from an industrial lineage of Streptomyces clavuligerus using comparative genomics, transcriptomics and phenotypic profiling for dynamic genome architectures with plasmid integration events and chromosomal rearrangements, alongside the accumulation of mutations affecting metabolic pathways and global gene regulation. These changes increased precursor supply and reprogrammed transcription leading to enhanced clavulanic acid production but reduced catabolic flexibility. Complementation experiments confirmed the functional impacts of specific mutations. These findings reveal that artificial selection shapes genome evolution in industrial strains, balancing production gains with metabolic trade-offs. This work will likely inform rational design of Streptomyces strains for improved natural product production in industry while highlighting the constraints imposed by domestication on metabolic versatility. More broadly it shows that many of the evolutionary processes in industrial strain improvement programmes mirror those at play during natural selection.

microbiology↗

bioRxiv2025

Evidence supporting the first secondary chromosome in actinobacteria as a hallmark of the Embleya genus

Embleya is a genus within the family Streptomycetaceae, a group of actinobacteria with outstanding capacity for production of specialised metabolites and a strikingly complex life cycle. In this work, we sequenced the complete genome of the new species Embleya australiensis MST-11070 and validated the assembly using optical mapping. The genome of E. australiensis MST-11070 consists of a 7.1 Mb linear chromosome and three additional replicons, including a 4.2 Mb linear replicon, EEC1, significantly larger than all previously described secondary replicons from bacteria. EEC1 is typified by its similar composition to the chromosome in terms of GC-content, codon usage and gene functions. It also carries terminal inverted repeats identical to the chromosome. EEC1 is enriched in biosynthetic gene clusters (BGCs), including the only copy of the BGCs for the spore pigment and the surfactant peptide SapB, metabolites essential for the organisms lifecycle. EEC1 contains an origin of replication with at least some chromosomal properties, and its replication is likely to depend on functions provided by chromosomally located genes. Further comparison of Embleya spp. genomes suggests that EEC1-like replicons are conserved across the genus, in contrast to other known large linear extrachromosomal replicons (megaplasmids) in the order. EEC1 is thus a hallmark of the Embleya genus and is central to its evolution within the Streptomycetaceae family. We propose EEC1 as a secondary chromosome, distinct from previously described secondary chromosomes that utilise plasmid-like replication mechanisms (chromids) and the largest secondary replicon reported in bacteria, to date.

genomics↗