Landornamides, antiviral ornithine-containing peptides discovered by proteusin mining
Proteusins are a family of post-translationally modified peptides that largely remain in silico-predicted. In a recent Angewandte Chemie article, the Piel and Oxenius groups (IMB) describe the first cyanobacterial proteusin representative named landornamide A with an intriguing antiviral activity.
The only known proteusin natural products prior to this study were the polytheonamide, potent cytotoxins with remarkably complex structures due to numerous unusual posttranslational modifications. Even though biosynthetic genes for potential further proteusins can be detected in a large number of cyanobacterial genomes, none of these natural products had been characterized to date. Interrogating whether this gene diversity offered biochemical and pharmacological discovery potential, the research groups characterized landornamide A from a Kamptonema sp. cyanobacterium, Since the gene cluster was silent when the organism was grown in the laboratory, the substance was produced through a synthetic biology strategy by reconstructing the pathway in E. coli. This revealed a new peptide combining lanthionines, D‐amino acids, and, as a novel posttranslational modification type, ornithines introduced by an arginase‐like enzyme. Landornamide A inhibited lymphocytic choriomeningitis virus infecting mouse fibrosarcoma cells, representing one of the few known anti‐arenaviral compounds. The data support proteusins as a rich resource of chemical scaffolds, new maturation enzymes, and bioactivities.
Link to the paper in external page Angewandte Chemie - International Edition.