A highly processive actinobacterial topoisomerase I – thoughts on Streptomyces’ demand for an enzyme with a unique C-terminal domain

Topoisomerase I (TopA) is an essential enzyme that is required to remove excess negative supercoils from chromosomal DNA. Actinobacteria encode unusual TopA homologues with a unique C-terminal domain that contains lysine repeats and confers high enzyme processivity. Interestingly, the longest stretch of lysine repeats was identified in TopA from Streptomyces , environmental bacteria that undergo complex differentiation and produce a plethora of secondary metabolites. In this review, we aim to discuss potential advantages of the lysine repeats in Streptomyces TopA. We speculate that the chromosome organization, transcriptional regulation and lifestyle of these species demand a highly processive but also fine-tuneable relaxase. We hypothesize that the unique TopA provides flexible control of chromosomal topology and globally regulates gene expression.