Bacterial Degradation of Microcystins and Nodularin

Abstract

Microcystins and nodularins produced by cyanobacteria are potent hepatotoxins and tumor promoters. They are, respectively, cyclic heptapeptides and cyclic pentapeptides containing a characteristic beta-amino acid residue, (2S,3S,8S,9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4(E ),6(E)-dienoic acid (Adda). Strain B-9 isolated from Lake Tsukui, Japan, degrades microcystin-LR, which is the most toxic among the microcystins, to nontoxic Adda as an end product. In the present study, we characterized the bacterial degradation process of the cyclic peptide hepatotoxins by liquid chromatography/ion trap tandem mass spectrometry. The use of protease inhibitors with a B-9 cell extract indicated that the degradation process of microcystin-LR consists of sequential enzymatic hydrolyses of Arg-Adda, Ala-Leu, and then Adda-Glu peptide bonds into two known nontoxic intermediate degradation products and then Adda, respectively. Subsequently, additional microcystins and nodularin were compared with microcystin-LR on substrate specificity. The cyclic peptides containing the Arg-Adda peptide bond were almost completely degraded to Adda as well as microcystin-LR, whereas microcystin-LF containing the Phe-Adda peptide bond instead of Arg-Adda peptide bond and 6(Z)-Adda-microcystin-LR and -RR which are geometrical isomers of the Adda residue were barely degraded. These results indicated that the degrading enzymes selectively hydrolyzed the Arg-Adda peptide bond as the initial ring opening of the cyclic peptide hepatotoxins, microcystins and nodularin.

Microbial biodegradation of microcystin-RR by bacterium Sphingopyxis sp. USTB-05

“…Adda is a characteristic β-amino acid (2S, 3S, 8S, 9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4(E), 6(E)-dienoic acid, which is essential to the toxicity of MC-RR. Previous studies revealed that Adda-Arg was the bond that was easily attacked during the enzymatic degradation by many bacteria (Bourne et al, 1996(Bourne et al, , 2001Imanishi et al, 2005). Ion with m/z 1056.9 may thus be derived from MC-RR by opening the ring through breaking the Adda-Arg bond and combining one hydrogen on the NH 2 group of Adda and a hydroxyl on the carboxyl group of arginine.…”

“…The tetrapeptide was finally degraded into Adda (Imanishi et al, 2005). The MC-RR biodegradation pathways by Sphingomonas sp.…”

Microbial degradation of cyclic peptides produced by bacteria

“…B-9 is a bacterial strain isolated from a eutrophicated lake and belongs to Sphingosinicella sp., which can hydrolyze MCs and nodularin using its intracellular enzymes. 3 An earlier study was carried out to investigate further the hydrolytic capabilities of the MC-degrading enzymes of B-9. 13 As a result of this investigation, it was confirmed that the enzymes can also hydrolyze the peptide bonds of several cyanobacterial cyclic peptides that were structurally different from the MCs and nodularin.…”

“…2 This strain showed a promising potential for the degradation of MC-related compounds and nodularin. 3 Such an MC-degrading bacterium was first isolated in Australia and was identified as one of the Sphingomonas strains (ACM-3962) in 1994. 4 Phenotypically, similar bacteria capable of degrading MC have been reported subsequently all over the world.…”

Isolation of a Arthrobacter sp. T11 that Degrades Cyanobacterial Hepatotoxin Microcystin from the Sediment of a Shallow Hypertrophic Lake

“…and Bacillus sp., have been regarded as excellent candidates for microcystindegrading properties [8][9][10][11]. In contract to several chemical treatments, biodegradation methods not only avoid producing carcinogenic substances and other mutagens, but also effectively remove microcystins [12].…”