Undecylprodigiosin

Takano, E., Gramajo, H.C., Strauch, E. et al. (1992) Transcriptional regulation of the redD transcriptional activator gene accounts for growth-phase-dependent production of the antibiotic undecylprodigiosin in Streptomyces coelicolor A3(2). Molecular Microbiology, 6, 2797-2804. 

A synthesis of the immunosuppressive agent undecylprodigiosine involved a Suzuki coupling between 57 and triflate 62 to give tripyrrole 63 [57]. The corresponding Stille reaction was unsuccessful... 

The ribosome-associated ppGpp synthetase (RelA) is required for antibiotic production under the conditions of nitrogen limitation in S. coelicolor A3 and for cephamycin C production in S. clavuligerus. Deletion of the relA in S. coelicolor A3 results in the loss of production of the antibiotics actinorhodin (Act) and undecylprodigiosin (Red) and... 

Recently, undecylprodigiosine (11) was reported to inhibit T-cell proliferation at doses that are not cytotoxic, which is particularly attractive with regard to its potential clinical application. The hitherto published total syntheses of prodigiosines involve several steps and are not suitable for scale-up in the case of possible lead structure development. D Alessio and Rossi [54] have devised a new synthetic pathway allowing the reproducible and consistent production of undecylprodigiosine (Eq. (26)). 

Streptomyces wild-type strain undecylprodigiosin producer... 

Cells carrying genes required for undecylprodigiosin production... 

Figure 5.8 Structure of prodigiosin 16, undecylprodigiosin 17, and related derivatives butyl-meffl-cycloheptylprodigiosin 18 and methylcyclodecylprodigiosin 19.

Figure 5.9 Biosynthetic origin of prodigiosin, undecylprodigiosin, and two cyclic derivatives, and labeling pattern from the incorporation of the labeled precursors [carfcoxy/- C]-DL-proline, [2- C] acetate, [3- C]-DL-serine, [2- C]glycine, [3- C]-L-alanine, and [mef/ty/- " C]-methionine.

The last step in the biosynthesis of undecylprodigiosin is the condensation of 2-undecylpyrrole with the bipyrrole MBC to complete the formation of the extended system of conjugated double bonds responsible for the characteristic red color of most prodigiosins (Figure 5.13) [65]. In that report, the authors were unable to assign a gene product to the catalysis of this reaction. However, since synthetic studies have shown that this reaction easily proceeds in the presence of a Bronsted acid catalyst, it was proposed that this reaction may not require catalysis by a pathway-specific enzyme in vivo. 

Figure 5.13 Coupling of 2-undecylpyirole and 4-methoxy-2,2 -bipyirole-5-carboxaldehyde to form undecylprodigiosin, and oxidative cyclization of undecylprodigiosin to give meto-butylcyclobeptylprodigiosin.

Figure 5.16 Latest proposal for the biosynthetic pathway to undecylprodigiosin. KS, ketosynthase CLF, chain-length factor ACP, acyl carrier protein ST, seryl transferase A, adenylation AT, acyltransferase and GT, PLP-dependent glycyl transferase.

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