Microviridin – the largest known cyanopeptide

Cyanobacterial blooms are a global problem for freshwater ecosystems because they are detrimental to water quality and affect the use of water bodies for recreational activities. They are also considered a growing public health concern due to production of biologically active secondary metabolites with toxic potential. Up to now, more than 600 cyanobacterial peptides are known and according to their chemical structure they can be divided in classes. Here, we present the class of Microviridins. The first microviridin was isolated from the cyanobacterial Microcystis viridis but it can also be produced by the cyanobacterial Planktothrix and Nostoc. Microviridins are the largest known cyanobacterial oligopeptides, and to date 16 variants have been characterized. This group is characterized by the multicyclic structure established by intramolecular amide or ester bonds and a side chain of variable length. The main peptide ring consists of seven amino acids with an ester bond between the 4-carboxy group of aspartate (position 10) and the hydroxyl group of threonine (position 4) and a peptide bond between the 6amino group of lysine (position 6) and the 4-carboxy group of glutamate (position 7). The structural variations are primarily due to substitutions in the side chain at position 5 in the ring.

Microviridins are potent and selective inhibitors of a variety of serine proteases including chymotrypsin, trypsin, and elastase. It was observed that the amino acid occupying the 10th position from the carboxylic end of the peptide is the one that selects for the type of serine proteases that is inhibited.4 Protease inhibition can lead to incomplete digestion of proteins what can lead into depletion of essential amino acids. In fact, microviridin J was found to be toxic to the crustacean Daphnia. As daphnids constitute a key group of organisms in freshwater ecosystems disturbance of these animals may have effects throughout the aquatic community.3 Those findings reinforce the need to consider not only the well-known class of microcystins but also other cyanobacterial peptides classes to do a proper risk assessment of cyanobacterial blooms.

References

1. Welker, M. & Von Döhren, H. (2006) Cyanobactcerial peptides – Nature’s own combinatorial biosynthesis. FEMS Microbiol Rev, 30:530-563.
2. Ishitsuka M.O et al. (1990) Microviridin. A novel tricyclic depsipeptide from the toxic cyanobacterium Microsystis viridis. J. Am. Chem. Soc, 112(22): 8180-8182.
3. Rohrlack, T et al. (2004) Cyanobacterial Protease Inhibitor Microviridin J Causes a Lethal Molting Disruption in Daphnia pulicaria. Applied and Environmental Microbiology, 70(8):5047–5050.
4. Murakami, M. et al. (1997) Microviridins, elastase inhibitors from the cyanobacterium Nostoc minutum (NIES-26). Phytochemistry, 45:1197–1202.

Figures

• Left: Modified from Welker et al., 2006.
• Right: Source: https://www.plantscience4u.com)