Naturally occurring lasso peptides as algicidal agents against Microcystis aeruginosa

The expansion of harmful cyanobacterial blooms (HCBs) worldwide over the past decades has been accompanied by growing environmental and societal concerns. Numerous strategies have been developed to control HCBs, among which algicidal substances produced by bacteria are one of the most promising and eco-friendly tools. In this study, we report a novel anti-cyanobacteria bioactive product, lasso peptides (LPs), derived from a microcystin-degrading bacterium, Novosphingobium sp. ERW19. Two types of LPs (designated novosphingonodin I and II) were expressed and isolated in an Escherichia coli-based heterologous expression system. Both LPs were strongly algicidal against Microcystis aeruginosa, a dominant species of HCBs. The maximum growth inhibition rates of the crude extracts of novosphingonodin I and II against M. aeruginosa were 42.38% and 49.36%, respectively. The physiological, morphological, and transcriptomic evidences indicated that the algicidal mechanism of LPs lay in disrupting the photosynthetic system of M. aeruginosa. Both LPs inhibited the growth of M. aeruginosa by reducing the Chl a content, destroying the thylakoid membranes, decreasing the maximum quantum yields, and triggering the downregulated expression of important photosynthetic genes, which led to the failure of photosynthesis. To the best of our knowledge, this is the first report on the algicidal activity of LPs against a bloom-forming species. Moreover, we demonstrated that the in vivo production of LPs is regulated by quorum sensing (QS), thus manipulation of the QS system may be a promising strategy to achieve efficient production of LPs for HCBs control.