Prodigiosin, biosynthesis

C-biosynthetic incorporation work established that acetate, glycine, proline, and methionine were prime precursors of prodigiosin. However, the structural complexity, sensitivity, and lability of this molecule made the isolation of fragments difficult. Studies on the mechanism of this biosynthesis were thus ideally suited to and amenable to the method. The mechanism of the pyrrole ring formation in prodigiosin biosynthesis is also unrelated to porphyrin biosynthesis and is thus of special interest. 

Santer, U. V. Prodigiosin biosynthesis in Serratia marcescens. Ph.D. Thesis 1958 Yale Univ., New Haven, Conn. 

Williams, R. P., and C. L. Gott Control of prodigiosin biosynthesis by temperature (Abstract), p. 24. VIII. Internatl. Cong. Microbiol. 1962c. 

Nakajima, M. Mechanism of prodigiosin biosynthesis. Bull. Osaka Med. School 11, 39 (1965a) [Chem. Abstr. 64, 20243 (1966)]. 

It has been observed that carbon from amino-acids capable of initiating biosynthesis of prodigiosin (202) in non-proliferating cells of 5. marascens is incorporated into (202). Some other amino-acids unable to act in this way were also incorporated after biosynthesis was initiated. 

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. 

The studies that allowed a revision of the synthetic pathway of prodigiosin also indicated that all the genes that identified were involved in the biosynthesis of MBC and have close homologs in the red cluster. However, none of the genes involved in the biosynthesis of MAP found its counterpart in the red cluster. This very strongly suggested that the biosynthesis of MBC is essentially the same in... 

Here, these alkaloids will be described in this chapter as alkaloids based on a porphine skeleton. Their biosynthesis is completely different from that of prodigiosin described in the chapter on alkaloids derived from proline (Chapter 5). Total synthesis of chlorophyll a was achieved [2,3], and the assignment of all resonances in the nuclear magnetic resonance (NMR) spectrum of chlorophyll b has been accomplished [4]. Also the biosynthesis and chemistry of the chlorophylls have been reviewed [5—8]. 

A strain of Streptomyces recognized as Str. olivaceus and isolated from a sample of soil obtained in Turkey was found to produce a family of peptidolipidic antibiotics along with prodigiosin and metacyclo-prodigiosin. These antibiotics interfered with the biosynthesis of murein and only the growth of actinomycetes was inhibited 123). 

The biosynthesis of asperlin (133), an antibiotic metabolite of Aspergillus nidulans (NRRL 3134), has been investigated by growing the culture in the presence of [l- C]acetate. Examination of the proton-noise-decoupled C n.m.r. spectrum (25.15 MHz) provided proof that the biosynthesis of asperlin involves linear condensation of four acetate units. Another example of the use of C n.m.r. spectroscopy in biosynthetic investigations has been provided by a recent report on the biosynthesis of prodigiosin (134). Previous studies had shown that radioactivity from acetate, glycine, proline, and methionine could be incorporated into prodigiosin. However, the specificity of the incorporation could not be determined because of the difficulties involved in small-scale... 

The biosynthesis of prodigiosin has been reviewed (Marchal, 1958 Las-CELLES, 1962 Bogorad, 1963 Carrera, 1963 Thimann, 1963). Some advances have been made since these reviews appeared, but the complete biosynthetic pathway for formation of prodigiosin remains a mystery. Biosynthesis is complex and involves two different pathways to the intermediate precursors, MBC and MAP, plus enzymatic couphng of the two to form prodigiosin (Fig. 2). Although... 

Fig. 2. Schema for biosynthesis of prodigiosin showing structure of intermediates that have been identified. Location of known mutants blocked in MBC or MAP pathways is shown by dotted lines. Unknown intermediates produced by certain mutants are...

Study of mutants has provided the most significant contributions to the biosynthesis of prodigiosin. Certain strains of S. marcescens, such as Hy, have a high spontaneous rate of mutation other strains, such as Nima, appear to be relatively stable. Bunting (1946) reviewed spontaneous color variants arising in S. marcescens. In 1953> Labrum and Bunting demonstrated that irradiation with... 

Mutants blocked at points 2, 3> 4 and 6 are reported in the literature and will be described below. Mutants blocked at points 1, 5 and 7 have been isolated (Williams and Gott, unpublished). Existence of mutants blocked at different points along each pathway indicates that biosynthesis of MAP and of MBC occurs in several enzymatic steps. Mutants blocked at point 7 cannot synthesize either MAP or MBC, but they will form prodigiosin if furnished with intermediates from mutants blocked at points 1, 2, 3, 4, 5 or 6 in either pathway. The isolation of these mutants suggests that an intermediate step common to both pathways exists and that perhaps prodigiosin is synthesized via a doubly bifurcated pathway. 

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