Diversity, Biosynthesis and Bioactivity of Aeruginosins, a Family of Cyanobacteria-Derived Nonribosomal Linear Tetrapeptides

Abstract

Aeruginosins, a family of nonribosomal linear tetrapeptides discovered from cyanobacteria and sponges, exhibit in vitro inhibitory activity on various types of serine proteases. This family is characterized by the existence of the 2-carboxy-6-hydroxy-octahydroindole (Choi) moiety occupied at the central position of the tetrapeptide. Aeruginosins have attracted much attention due to their special structures and unique bioactivities. Although many studies on aeruginosins have been published, there has not yet been a comprehensive review that summarizes the diverse research ranging from biogenesis, structural characterization and biosynthesis to bioactivity. In this review, we provide an overview of the source, chemical structure as well as spectrum of bioactivities of aeruginosins. Furthermore, possible opportunities for future research and development of aeruginosins were discussed.

High Structural Diversity of Aeruginosins in Bloom-Forming Cyanobacteria of the Genus Planktothrix as a Consequence of Multiple Recombination Events

“…In general, Aer peptides have been found bioactive because of proteolytic enzyme inhibition (i.e., serine proteases such as trypsin, thrombin, plasmin) effective in the nanomolar to lower micromolar range (e.g., [2][3][4][5]). We tested the toxicity of the variants Aer 716 ([M+H] + 717.3 from No1020), Aer 688 ([M+H] + 689.3 from NIVA-CYA116) and Aer 828A ([M+H] + 829.3 from No91/1) using a standard toxicity assay (i.e., the anostracan crustacean Thamnocephalus platyurus).…”

“…The aeruginosins (Aer) constitute a bioactive peptide family that is found widely distributed among marine and freshwater cyanobacteria [1], and also among higher organisms such as marine sponges of the family Dysideidae [2,3]. The structural diversity of Aer is intriguingly high, and structure-function relationships have been used to understand the consequences for inhibition of serine proteases and other enzymes [4,5].…”

“…In particular, the Aer peptide family has the highest structural variability [7,8]. Other Aer peptide producers include the genera Microcystis, Nostoc, Nodularia [3,9] and Spaerocarvum [10]. Aer synthesis is encoded by aer genes, organized into a biosynthetic gene cluster (aer BGC) encoding several non-ribosomal peptide synthetases (NRPS), which are responsible for specific amino acid recognition and incorporation.…”

My 50-Plus Years of Academic Research Collaborations with Industry. A Retrospective

“…The aeruginosins are cyanobacterial glycopeptides isolated from marine sources in different parts of the world. , Dysinosin A ( 18 ), a new member of the family, was isolated from an Australian marine sponge by Quinn in 2002 who obtained a cocrystal structure in complex with the enzyme thrombin (Factor IIA) and Factor VIIA (Scheme ). The inhibitory activity of dysinosin A against thrombin and Factor VIIA, which are essential enzymes in the blood coagulation cascade leading to blood clot formation was of interest in view the antithrombotics program at AstraZeneca in Mölndal.…”