The biosynthesis and regulation of bacterial prodiginines

Abstract

The red-pigmented prodiginines are bioactive secondary metabolites produced by both Gram-negative and Gram-positive bacteria. Recently, these tripyrrole molecules have received renewed attention owing to reported immunosuppressive and anticancer properties. The enzymes involved in the biosynthetic pathways for the production of two of these molecules, prodigiosin and undecylprodigiosin, are now known. However, the biochemistry of some of the reactions is still poorly understood. The physiology and regulation of prodiginine production in Serratia and Streptomyces are now well understood, although the biological role of these pigments in the producer organisms remains unclear. However, research into the biology of pigment production will stimulate interest in the bioengineering of strains to synthesize useful prodiginine derivatives.

YgfX (CptA) is a multimeric membrane protein that interacts with the succinate dehydrogenase assembly factor SdhE (YgfY)

“…Pig is ultimately produced from the condensation of the terminal products from the MAP and MBC biosynthetic pathways (Williamson et al, 2005(Williamson et al, , 2006. Interestingly, PigB is an FAD-containing inner-membrane protein that catalyses the terminal reaction in MAP biosynthesis, whilst PigC is responsible for the final condensation reaction (Williamson et al, 2005).…”

“…Interestingly, PigB is an FAD-containing inner-membrane protein that catalyses the terminal reaction in MAP biosynthesis, whilst PigC is responsible for the final condensation reaction (Williamson et al, 2005). PigN catalyses the terminal step in MBC synthesis and is also predicted to be membrane bound (Williamson et al, 2006). It is possible that, in addition to indirect transcriptional activation of pigA-O, YgfX might facilitate the formation of a terminal pig biosynthetic complex consisting of PigB and PigC.…”

Carbon source regulation of antibiotic production

“…It is known that biosynthesis of both compounds (that is, carbapenem and prodigiosin) are under quorumsensing control. 32,33 These secondary metabolites are controlled by the smaR quorum-sensing locus, which represses both compounds when levels of N-acyl-homoserine lactone are low. Quorum sensing controls the production of prodigiosin, at least in part, by modulating transcription of three genes encoding regulatory proteins.…”

Characterization of a broad-host-range flagellum-dependent phage that mediates high-efficiency generalized transduction in, and between, Serratia and Pantoea

“…Prodigiosins, as prodiginines, have a diverse range of biological activities (Williamson et al, 2006), but it is their anti-cancer activity that is currently being investigated in clinical trials (Nguyen et al, 2007). The biosynthesis and regulation of prodigiosin have been studied in some detail (Thomson et al, 2000;Williamson et al, 2005;Slater et al, 2003;Fineran et al, 2005aFineran et al, , b, 2007, and some of this work has been facilitated by the facile construction of double and triple mutant strains using WOT8.…”