The Line of Duty: how to maintain a giant linear plasmid in antibiotic-producing Streptomyces 

LE_J22DTP

The majority of bacterial plasmids are circular, linear plasmids are rare. However, giant linear plasmids are widely distributed in the antibiotic producing genus Streptomyces. This genus accounts for ~80% of antibiotic compounds known today and therefore an understanding of the genetic makeup of this genus is important in the context of antibiotic resistance.

Linear plasmids in Streptomyces are involved in antibiotic production, degradation of aromatic compounds, and in phyto-pathogenicity. For example, the 350-kb linear SCP1 plasmid of Streptomyces coelicolor A3(2) carries the biosynthetic cluster for methylenomycin antibiotic. Accumulated data suggest that giant linear plasmids have played critical roles in the horizontal transfer of secondary metabolism and evolution of Streptomyces genomes. Given the biological significance of these linear plasmids, it is surprising that little is known about how these plasmids get transmitted to the daughter cells, and how they might co-exist with the linear chromosome of the host.

Motivated by the recent works in our lab on solving the 3D organization of a linear Streptomyces venezuelae chromosome, and on elucidating the mechanism of chromosome segregation by the ParA-ParB-parS system, we aim to better understand the molecular mechanism responsible for the segregation and inheritance of the giant linear plasmid SCP1 in Streptomyces coelicolor A3(2).

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References

1. Szafran, M. J. et al. Spatial rearrangement of the Streptomyces venezuelae linear chromosome during sporogenic development. bioRxiv 2020.12.09.403915 (2020) doi: 10.1101/2020.12.09.403915 (in press in Nature Communications).

2. Jalal, A. S. et al. A CTP-dependent gating mechanism enables ParB spreading on DNA. Elife 10, e69676 (2021).

3. Kinashi, H. Giant linear plasmids in Streptomyces: a treasure trove of antibiotic biosynthetic clusters. J Antibiot 64, 19–25 (2011).