P-Methylaspartate

Freshwater cyanobacteria Microcystis, Oscillatoria, Ana-baena, and Nostoc produce several types of toxins, among which the most commonly detected are the hepatotoxic peptides microcystins. The general structure of the microcystins is cyclo-(D-Ala -X -D-MeAsp -Z -Adda -D-Glu -Mdha ), in which X and Z represent variable L-amino acids, D-MeAsp is D-eryf/iro-p-methylaspartic acid, Mdha is A-methyldehydroalanine, and Adda is the unusual C20 amino acid, (25,35,85,95)-3-amino-9-meth-oxy-2,6,8-trimethyl-10-phenyldeca-4( ),6( )-dienoic acid (Fig. 1). The structural differences in the microcystins mainly depend on the variability of the two L-amino acids (denoted X and Z), and secondarily on the methylation or demethylation of D-MeAsp and/or Mdha. More than 60 microcystins have been isolated from bloom samples and isolated strains of cyanobacteria. 

While the 2-oxobutyrate needed for isoleucine formation is shown as originating from threonine in Eig. 24-17, bacteria can often make it in other ways, e.g., from glutamate via p-methylaspartate (Eig. 24-8) and transamination to the corresponding 2-oxoacid. It can also be made from pyruvate by chain elongation using acetyl-CoA (Eig. 17-18) citramalate and mesa-conate (Eig. 24-8) are intermediates. This latter pathway is used by some methanogens as are other alternative routes. The first step unique to the biosynthetic pathway to leucine is the reaction of the... 

Microcystins constitute a large family of cyclic heptapeptides with a high degree of homology in the amino acid sequence. As shown in Fig. 4, they are composed of D-Ala in position 1, two variable L-amino acids at positions 2 and 4, the 3-linked D-e/yt/iro-P-methylaspartic acid (MeAsp) in position 3, the novel C20 P-amino acid (25,35,85,95) - 3 - amino - 9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid... 

Fig. (1) shows the retrosynthetic approch proposed by Schreiber. The 19-raembered pentapeptide macrocycle of motuporin was initially disconnected at the ( -valine iso-D-erytro-P-methylaspartate amide bond. The (N-methylamino)-dehydrobutyrate residue (mdhb) was masked... 

The first chemical stractures of cyanobacterial cyclic peptide toxins were identified in the early 1980s and the number of fully characterized toxin variants has greatly increased since the 1990s. To-date there are 77 different microcystins isolated from cyanobacteria (Table 40.3). The first such compounds found in freshwater cyanobacteria were cyclic heptapeptides with the general stracture of cyclo-(D-alanine -X -D-MeAsp -Z" -Adda -D-Glutamate -Mdha ) in which X and Z are variable amino acids, o-MeAsp is D-eryt/jro-p-methylaspartic acid, and Mdha is A-methyldehydroalanine (Eigure 40.1a). The amino acid Adda, (2S, 3S, 8S, 9S)-3-amino-9-methoxy-2,6,8- trimethyl-10-phenyldeca-4,6-dienoic acid, is the most unusual structural moiety in... 

Amino-acid analogs and uncommon L-amino acids W-acetyl-aspartate, W-acetyl-serine, oi-amino-n-butyrate, 3-aminoisobutyrate, aspartate ethyl or methyl ester, citrulline, cysteate, fumarate, glutathione, homoserine, erythro- and threo-p-hydroxyaspartate, isoasparagine, isoserine, malate, a- and p-methylaspartate, methylserine, phenol, serine amide, serine methyl ester, succinate [498, 747]... 

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