3- amino-9-methoxy-2,6,8-trimethyl-1 phenyl-4,6-decadienoic acid

Figure 7.26 The structure of the hepatotoxic cyclic heptapeptide microcystin LR. L-Arginine and L-leucine are variable amino acids. The reactive unsaturated group is indicated by the star. Abbreviations Adda, amino-methoxy-trimethyl-phenyl-decadienoic acid Mdha, methyldehydro-alanine Masp, methyl D-/so-aspartate D-Glu, D-/soglutamate D-Ala, D-alanine.

Adda — (2 5, 35, 85, 95)-3-Amino-9-methoxy-trimethyl- 10-phenyl-4,6-decadienoic acid... 

Figure 39.1a shows the generic structure of microcystins (MC), with the two most variable positions marked by X and Z. The numbering of the individual positions was done before the elucidation of the biosynthetical pathway and is arbitrary (see below). MCs are cyclic heptapeptides with several structural peculiarities. The moiety characteristic of microcystins and nodularins is the Adda, abbreviated for 3-amino-9-methoxy-2,6,8,-trimethyl-10-phenyl-4,6-decadienoic acid, a P-amino acid that is not known from other natural products. Further peculiarities of the molecule are o-amino acids. These stereoisomers of commonly occurring L-amino acids are not found in ribosomally synthesized proteins and peptides and are therefore called nonproteinogenic amino acids. A-methyl-dehydroalanine (Mdha) in position 7 also is a nonproteinogenic amino acid as it is the case with o-erythro-P-methyl-iso-aspartate (o-MeAsp). 

The part of the molecule inside the dotted box, which is common to all of the microcystins, is 3(S)-amino-9(S)-methoxy-2(S),6,8(S)-trimethyl-10-phenyl-4,6-decadienoic acid, usually known as Adda. The most widespread microcystins are as follows microcystin-LA, -LR, -RR, -YA, -YM, and -YR, but there are many others (Namikoshi et al, 1995). An article on the toxicology of microcystins was published by Dawson in 1998, and some microcystins have been characterized from Antarctic cyanobacterial mats (Jungblut et al, 2006). For the detection of microcystins in cells and water, see Lawton, Edwards, and Codd, 1994 Lawton and Edwards, 2008 Lawton et al, 2010. 

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