Proline prodigiosin

Prodigiosin.—The formation159 of prodigiosin (162) from intact molecules of L-proline and L-alanine (but with loss of the carboxy-group) has been confirmed160 by... 

Streptomyces showdoensis incorporates 95% 1-[ C] or 2-[ C]acetate into showdomycin (1) in the maleimide ring only [22], and this confirms earlier C findings. The exclusive incorporation of l-[ C]acetate at C-1, and 2-[ C]acetate at C-2, C-3 and C-4 can be explained with reference to the Krebs cycle and the malic enzyme. C Spectra on 0.1 M solutions of labelled showdomycin in 13 mm tubes required 6 hr accumulation time. Furthermore, C-labelled alanine, proline, glycine and serine have been fed to the bacterium Serratia marcescens [23] to trace the origin of the carbon atoms in its tripyrrole metabolite, prodigiosin (2). The methoxy group is probably derived from methionine whereas the C-2 methyl is from alanine. 

Prodigiosins.—The tripyrrole skeleton found in prodigiosin (202), produced by Serratia marescens, is also found in (203) and (204), produced by Streptomyces longisporus ruber. As a result of feeding experiments with C-labelled precursors a unique pathway to (202) was revealed, for which the building blocks are acetate, alanine, serine, and proline. Similar experiments in S. longisporus ruber have indicated clearly that the pathway used for the elaboration of (203) and (204) in vivo is closely related to that which affords (202). 

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.

In this chapter, prodigiosin, obtained from the cultured broth of Serratia marcescens stachydrine, isolated from Fabaceae plants and pyrrole-2-carboxyUc acid, isolated from the culture broth of Streptomyces sp. No. 82-85 are described. Regarding these alkaloids, it was established that labeled prohne is incorporated into these alkaloids. It was also determined that alanine and glycine are incorporated into prodigiosin, in addition to proline [1]. However, intact incorporation of proline into prodigiosin as a unit retaining the nitrc en atom was observed, and consequendy this alkaloid is described in this chapter. 

Three pyrrole nuclei exist in prodigiosin, and it was shown that one of these units is derived from proline. In addition, a C2 unit originated from... 

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]. 

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... 

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. 

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