18 March 2019

Microginin – a toxin or a potential drug?

Figure 1:Microcystis aeruginosa

Cyanobacteria produce a vast array of unique and bioactive linear and cyclic peptides. In addition to the well-known hepatotoxic class of microcystins, those cyanopeptides can be classified in other 5 classes1. Here, we present the class of Microginin. Microginin has been first isolated from the cyanobacteria Microcystis aeruginosa (Figure 1) and can also be produced by other cyanobacteria genera such as Planktothrix, Oscillatoria and Nostoc.

Microginin is a class of linear peptide that is characterized by the presence of the Ahda (3-amino-2-hydroxydecanoic acid) moiety and a predominance of two tyrosine units at the C-terminus (Figure 2). Microginins vary in length from four to six amino acids with molecular weight ranging from 574 to 930 Da. Apart from the Ahda all the other positions are variable with position 2 being the most variable with seven amino acids reported.

Figure 2: Chemical structure of Microginin 713 representative of the general chemical structure of the microginin class characterized by the Ahda moiety (1). Variation in the other moieties are listed as the three-letter code of canonical amino acids and other modifications (Cl, chlorination; N-methyl, N-methylation) (Janssen, 2019).

The physiological functions of cyanopeptides in general is not fully understood. The class of microginin was reported to show both ecotoxicological effects and pharmacological potential.

Members of the microginin class have been shown to be strong protease inhibitors with reported activity against angiotensin-converting enzyme (ACE), leucine aminopeptidase, aminopeptidase M, bovine aminopeptidase N, and trypsin3,4. ACE inhibitors is one of the most effective chemotherapy against hypertension and congestive heart failure, which makes microginin a potential candidate for the development of anti-hypertensive drugs. It is hypothesized that both the dityrosine unit as well as the Ahda moiety play an important role in ACE inhibition of microginin-type peptide3.

Microginin was also found to display biological activity against grazers. Microginin FR3 (MG-FR3) showed activity against the crustacean Thamnocephalus platyurus (LC50 = 7.78 µg.mL-1). However, MG-FR3 did not affect the activity of digestive proteases such as trypsin, chemotrypsin, and elastase, which indicates another mode of action2.

The class of microginin it is indeed a very interesting class of biological active molecules due to its ecotoxicological effect and pharmacological potential. However, more studies are necessary to better understand their mode of action, to define their potential ecological and human toxicity and to further explore their use as anti-hypertensive drug.

SMILES: OC1=CC=C(CC(NC(C(N(C)C(C(C(C)C)NC(C(NC(C(C(CCCCCC)N)O)=O)C)=O)=O)CC(C=C2)=CC=C2O)=O)C(O)=O)C=C1

References:

  1. Janssen, E.M.-L. (2019) Cyanobacterial peptides beyond microcystins – A review on co-occurrence, toxicity, and challenges for risk assessment. Water Research, 151:488-499.
  2. Bober, B. & Bialczyk, J. (2017) Determination of the toxicity of the freshwater cyanobacterium Woronichinia naegeliana (Unger) Elenkin. J.Appl.Phycol, 29:1355-1362.
  3. Ishida, K. et al. (2000) Microginins, zinc metalloproteases inhibitors from the cyanobacterium Microcystis aeruginosa. Tetrahedron, 56:8643-8656.
  4. Strangman, W.K. & Wright, J.L.C. (2016) Microginins 680,646 and 612 – new chlorinated Ahoa-containing peptides from a strain of cultured Microcystis aeruginosa. Tetrahedron Letters, 57:1801-1803.

 Photo credits:

  1. Figure 1:  https://commons.wikimedia.org/wiki/File:Microcystis_aeruginosa.jpeg
    Kristian Peters http://www.korseby.net/outer/flora/algae/index.html [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0)]