Pyrroles biosynthetic pathways

By 2D TOCSY NMR spectroscopy (TOCSY - total correlated spectroscopy), the structure of a biosynthetic intermediate of PQQ was shown to be 3a-(2-amino-2-carboxyethyl)-4,5-dioxo-4,5,6,7,8,9-hexahydroquinoline-7,9-dicarboxylic acid 15, not its constitutional isomer 16 <2004JA3452>. This result shows that the last enzyme on the biosynthetic pathway of PQQ facilitates a pyrrole ring closure and an unprecedented eight-electron oxidation of 15. 

Figure 1 shows the general structure of calixpyrroles. The basic ring structure resembles that of porphyrin. In the past, four pyrrole rings linked by methylene groups to form colourless macrocycles (that feature in the biosynthetic pathways to pyrrole pigments) were referred to as porphyrinogens [22], The term calix[4]pyrrole was later ascribed to these macrocycles and their synthetic derivatives because of their relation to calix[4]arenes [23],... 

An example of this approach is demonstrated in an antibody mimic of the enzyme ferrochetalase (39). Ferrochelatase catalyzes the insertion of Fe + into protoporphyrin IX (3) as the last step in the heme biosynthetic pathway (40). Interestingly, N-alkylporphyrins are known to be potent inhibitors of this enzyme, because alkylation at one pyrrole lutrogen distorts the planarity of the porphyrin macrocycle (41). This finding was used in the design of hapten 4 to catalyze the incorporation of metal ions into mesoporphyrin IX (5) by eliciting an antibody that binds the substrate in a ring-strained conformation. 

Pyrrolnitrin possesses a structure in which the benzene and pyrrole rings are attached and substituted by nitro and chlorine units [3]. Because of the unusual structure, the biosynthetic pathway became of interest, and Gorman and Lively proposed a biogenesis of pyrrolnitrin from tryptophan [2]. Studies using various stable and unstable isotopes were conducted using P. aureofaciens, which also produces pyrrolnitrin. As a result, it was shown that the skeleton of pyrrolnitrin originated from tryptophan, and that D-tryptophan was incorporated better than L-tryptophan. Namely, when [2- H, tryptophan was fed, it was clarified that the... 

It was mentioned above that the carboxyl carbon is lost in the conversion of anthranilic acid to indole. Consequently, two additional carbon atoms must be supplied to complete the pyrrole ring of the indole. The observation that various ribose derivatives could be the source of these two carbons provided the clue that led to the elucidation of the mechanism of indole synthesis in the tryptophan biosynthetic pathway (232). Yanofsky determined that sonic extracts of a tryptophan auxotroph of E. cdi (that also grew on anthranilic acid or indole) could utilize ribose, ribose 5-phosphate, and 5-phosphoribosylpyrophosphate to form indole from anthranilic acid. With the two former compounds, ATP was essential for the reaction, with the latter compound it was not. This result made it appear evident that 5-phosphoribosylpyrophosphate was the more immediate reactant in the condensation with anthranilic acid. 

Lastly, styhssazoles A-C are new complex pyrrole-2-aminoimidazole alkaloids (P-2-AI) that were isolated from Stylissa carteri collected in the Solomon Islands (Patel et al, 2010). These findings confirm the proposed universal biosynthetic pathway for all currently known dimeric P-2-AI compotmds (Al-Mourabit and Potier, 2001 Kock et al, 2007). 

These studies support the proposal that the enzyme chloroperoxidase initiates the biosynthesis by chlorinating the -indole or C-4 carbon of tryptophan, followed by formation of a new pyrrole ring and loss of the chlorine atom (Scheme 11). This route (pathway a) includes the penultimate step of chlorination of both aromatic rings before the oxidative conversion of the aromatic amino-group into a nitro-group. This biosynthetic proposal requires electrophilic chlorination of the 3-position of the pyrrole ring, which normally reacts with electrophiles at C-2 or C-5. 

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