Biosynthesis Prodigiosin

figure 1: structure of prodigiosin 1 highlighting a, b, , c pyrrole rings

the biosynthesis of prodigiosin involves convergent coupling of 3 pyrrole type rings (labeled a, b, , c in figure 1) l-proline, l-serine, l-methionine, pyruvate, , 2-octenal.

ring synthesized l-proline through nonribosomal peptide synthase (nrps) pathway (figure 2), wherein pyrrolidine ring of proline oxidized twice through fad+ yield pyrrole ring a.

ring expanded via polyketide synthase pathway incorporate l-serine ring b (figure 3). ring fragment transferred peptidyl carrier protein (pcp) acyl carrier protein (acp) ks domain, followed transfer malonyl-acp via decarboxylative claisen condensation. fragment able react masked carbanion formed plp mediated decarboxylation of l-serine, cyclizes in dehydration reaction yield second pyrrole ring. intermediate modified methylation (which incorporates methyl group l-methionine onto alcohol @ 6 position) , oxidation of primary alcohol aldehyde yield core a-b ring structure.

ring c formed tpp mediated decarboxylative addition of pyruvate 2-octenal, followed reaction plp generate amine intramolecular condensation. oxidation of resulting ring yields final pyrrole ring c.

finally, these 2 pieces stitched in dehydration reaction driven forward establishment of conjugated system across 3 rings. completes convergent synthesis of natural product.