The Serratia gene cluster encoding biosynthesis of the red antibiotic, prodigiosin, shows species- and strain-dependent genome context variation

Abstract

The prodigiosin biosynthesis gene cluster (pig cluster) from two strains of Serratia (S. marcescens ATCC 274 and Serratia sp. ATCC 39006) has been cloned, sequenced and expressed in heterologous hosts. Sequence analysis of the respective pig clusters revealed 14 ORFs in S. marcescens ATCC 274 and 15 ORFs in Serratia sp. ATCC 39006. In each Serratia species, predicted gene products showed similarity to polyketide synthases (PKSs), non-ribosomal peptide synthases (NRPSs) and the Red proteins of Streptomyces coelicolor A3(2). Comparisons between the two Serratia pig clusters and the red cluster from Str. coelicolor A3(2) revealed some important differences. A modified scheme for the biosynthesis of prodigiosin, based on the pathway recently suggested for the synthesis of undecylprodigiosin, is proposed. The distribution of the pig cluster within several Serratia sp. isolates is demonstrated and the presence of cryptic clusters in some strains shown. The pig cluster of Serratia marcescens ATCC 274 is flanked by cueR and copA homologues and this configuration is demonstrated in several S. marcescens strains, whilst these genes are contiguous in strains lacking the pig cluster.

Bacterial Biosynthetic Gene Clusters Encoding the Anti-cancer Haterumalide Class of Molecules

“…Random mutagenesis was then employed as a second strategy to isolate S. marcescens MSU97 mutants with reduced antimicrobial activity toward the oomycete P. ultimum. However, the MSU97 strain proved to be recalcitrant to various genetic tools that we have previously used successfully for the genetic analysis of secondary metabolite production in Serratia and Erwinia (36,47,49). This genetic intractability, coupled with high intrinsic multidrug resistance, made a classical mutagenesis approach unfeasible.…”

Prodigiosin biosynthesis gene cluster in the roseophilin producer Streptomyces griseoviridis

“…14 No role has been assigned to redS in the prodigiosin pathway and only the 146 aa N-terminal region of PigB (671 aa) shows sequence similarity with RedS. 7 In Serratia sp., PigB catalyzes the formation of 2-methyl-3-n-amylpyrrole (MAP), which is replaced by 2-undecylpyrrole in S. coelicolor. 14 No role has been assigned to redC or to redE, and no homologous genes have been found in the pig cluster in Serratia sp.…”

“…ATCC 39006. 7,8 PCR amplification of S. griseoviridis genomic DNA gave a redN/pigH-like gene fragment. Nucleotide sequencing and homology search showed that the fragment shared amino acid identity of 84% with RedN.…”

“…Prodigiosin-family biosynthesis genes have been reported to exist in the pig gene clusters in Serratia marcescens ATCC 274 and Serratia sp. ATCC 39006 (which make prodigiosin itself), 7 in the red gene cluster in S. coelicolor A3(2) (which makes undecylprodiginine) 8 and in the hap gene cluster in Hahella chejuensis KCTC 2396 (which makes prodigiosin itself). 9 PCR amplification of S. griseoviridis genomic DNA has identified genes homologous to redH, redM and redW, involved in the biosynthesis of undecylprodiginine in S. coelicolor ( Figure 2).…”

Production, Extraction and Characterization of Red Pigment Produced by Serratia rubidaea JCM 1240T isolated from Soil

“…Prodigiosin (PDG) is a natural red pigment characterized by a common pyrrolylpyrromethane skeleton, having low molecular weight (323.4 Dalton), appearing only in the late stages of bacterial growth as secondary metabolite (Harris et al, 2004) and produced by many bacterial species, including many strains of Serratia marcescens, Hahella chejuensis, Streptomyces variegatus, Colwellia (Vibrio) psychrerythraea, "Pseudomonas magnesiorubera, and other eubacteria (Yamamoto et al, 1999). The prodiginine group, of which prodigiosin is a member, is a group of structural isomers that contain a tripyrrole core with different alkyl chains, have no defined role in the physiology of producing strains but have been reported to have antifungal, antibacterial, algicidal, antiprotozoal, antimalarial, immunosuppressive, anticancer and antiproliferative activities (Castro, 1967;Boger and Patel, 1988;Williams and Quadri, 1980;Demain, 1995;Han et al, 1998;Cerdeno et al, 2001;Furstner, 2003;Pe´rez-Toma´s 2003and Samrot et al, 2011).…”