Biosynthesis of prodigiosin.  Incorporation patterns of carbon-13-labeled alanine, proline, glycine, and serine elucidated by Fourier transform nuclear magnetic resonance

Wasserman, H. H.; Sykes, R. J.; Peverada, P.; Shaw, Coralie; Cushley, Robert J.; Lipsky, S. R.

doi:10.1021/ja00801a080

Cited by 61 publications

(44 citation statements)

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“…The derivation of C‐2 of MAP and its attached methyl group from pyruvate instead of from alanine is fully consistent with the previously reported incorporation of 14 C‐ and 13 C‐labelled alanine, as alanine can readily be converted to pyruvate by a cellular transamination reaction (Wasserman et al ., 1973).…”

Section: Discussionsupporting

confidence: 90%

Biosynthesis of the red antibiotic, prodigiosin, in Serratia: identification of a novel 2‐methyl‐3‐n‐amyl‐pyrrole (MAP) assembly pathway, definition of the terminal condensing enzyme, and implications for undecylprodigiosin biosynthesis in Streptomyces

Williamson

Simonsen

Ahmed

et al. 2005

Molecular Microbiology

211

241

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SummaryThe biosynthetic pathway of the red-pigmented antibiotic, prodigiosin, produced by Serratia sp. is known to involve separate pathways for the production of the monopyrrole, 2-methyl-3-n-amyl-pyrrole (MAP) and the bipyrrole, 4-methoxy-2,2 ¢ -bipyrrole-5-carbaldehyde (MBC) which are then coupled in the final condensation step. We have previously reported the cloning, sequencing and heterologous expression of the pig cluster responsible for prodigiosin biosynthesis in two Serratia sp. In this article we report the creation of in-frame deletions or insertions in every biosynthetic gene in the cluster from Serratia sp. ATCC 39006. The biosynthetic intermediates accumulating in each mutant have been analysed by LC-MS, cross-feeding and genetic complementation studies. Based on these results we assign specific roles in the biosynthesis of MBC to the following Pig proteins: PigI, PigG, PigA, PigJ, PigH, PigM, PigF and PigN. We report a novel pathway for the biosynthesis of MAP, involving PigD, PigE and PigB. We also report a new chemical synthesis of MAP and one of its precursors, 3-acetyloctanal. Finally, we identify the condensing enzyme as PigC. We reassess the existing literature and discuss the significance of the results for the biosynthesis of undecylprodigiosin by the Red cluster in Streptomyces coelicolor A3(2).

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Section: Discussionsupporting

confidence: 90%

Biosynthesis of the red antibiotic, prodigiosin, in Serratia: identification of a novel 2‐methyl‐3‐n‐amyl‐pyrrole (MAP) assembly pathway, definition of the terminal condensing enzyme, and implications for undecylprodigiosin biosynthesis in Streptomyces

Williamson

Simonsen

Ahmed

et al. 2005

Molecular Microbiology

211

241

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“…The varying duration of intense pigmentation suggests that in addition to quorum sensing other regulatory elements control pigment synthesis. Prodigiosin synthesis requires precursors like L-proline, acetate, L-serine, S-adenosylmethionine, and 2-octenal (Quadri and Williams, 1973; Wasserman et al, 1973; Williamson et al, 2006). Since none are present in the M9 medium, V. ruber must synthesise them de novo .…”

Section: Discussionmentioning

confidence: 99%

Viscosity dictates metabolic activity of Vibrio ruber

Borić¹,

Danevčič²,

Stopar³

2012

Front. Microbio.

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Little is known about metabolic activity of bacteria, when viscosity of their environment changes. In this work, bacterial metabolic activity in media with viscosity ranging from 0.8 to 29.4 mPas was studied. Viscosities up to 2.4 mPas did not affect metabolic activity of Vibrio ruber. On the other hand, at 29.4 mPas respiration rate and total dehydrogenase activity increased 8 and 4-fold, respectively. The activity of glucose-6-phosphate dehydrogenase (GPD) increased up to 13-fold at higher viscosities. However, intensified metabolic activity did not result in faster growth rate. Increased viscosity delayed the onset as well as the duration of biosynthesis of prodigiosin. As an adaptation to viscous environment V. ruber increased metabolic flux through the pentose phosphate pathway and reduced synthesis of a secondary metabolite. In addition, V. ruber was able to modify the viscosity of its environment.

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“…In addition, the pigX mutant displayed decreased levels of AspA, an enzyme required for L-aspartate metabolism (L-aspartate is linked to serine and glycine biosynthesis) (37). Serine and proline are precursors in the biosynthetic pathway of prodigiosin (54). It is possible that the elevated level of SerC, which catalyzes the second step of serine biosynthesis (37), provides increased serine for the overproduction of pigment in the pigX background.…”

Section: Discussionmentioning

confidence: 99%

Virulence and Prodigiosin Antibiotic Biosynthesis inSerratiaAre Regulated Pleiotropically by the GGDEF/EAL Domain Protein, PigX

et al. 2007

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Gram-negative bacteria of the genus Serratia are opportunistic human, plant, and insect pathogens. Serratia sp. strain ATCC 39006 secretes pectinases and cellulases and produces the secondary metabolites carbapenem and prodigiosin. Mutation of a gene (pigX) resulted in an extremely pleiotropic phenotype: prodigiosin antibiotic biosynthesis, plant virulence, and pectinase production were all elevated. PigX controlled secondary metabolism by repressing the transcription of the target prodigiosin biosynthetic operon (pigA-pigO). The transcriptional start site of pigX was determined, and pigX expression occurred in parallel with Pig production. Detailed quantitative intracellular proteome analyses enabled the identification of numerous downstream targets of PigX, including OpgG, mutation of which reduced the production of the plant cell wall-degrading enzymes and virulence. The highly pleiotropic PigX regulator contains GGDEF and EAL domains with noncanonical motifs and is predicted to be membrane associated. Genetic evidence suggests that PigX might function as a cyclic dimeric GMP phosphodiesterase. This is the first characterization of a GGDEF and EAL domain protein in Serratia and the first example of the regulation of antibiotic production by a GGDEF/EAL domain protein.Gram-negative bacteria of the genus Serratia are members of the family Enterobacteriaceae (22). Some species, such as Serratia marcescens, are becoming a major cause of nosocomial infections (25) and are often difficult to treat due to the prevalence of resistance to multiple antibiotics (48). Serratia sp. strain ATCC 39006 was originally isolated from a salt marsh in Cheesequake, NJ, by E. R. Squibb and Sons, Inc., in an effort to mine producers of novel antibiotics (39). In common with certain S. marcescens strains, Serratia strain ATCC 39006 produces the red, linear tripyrrole pigment prodigiosin (Pig; 2-methyl-3-pentyl-6-methoxyprodigiosin), a secondary metabolite with antimicrobial, immunosuppressant, and anticancer properties (56). Indeed, Pig is in preclinical anticancer trials, and a derivative is in phase I/II clinical trials as an anticancer agent (56). A simple ␤-lactam antibiotic, carbapenem (Car; 1-carbapen-2-em-3-carboxylic acid) (14), and plant cell wall-degrading exoenzymes (47) are also produced by Serratia strain ATCC 39006. Serratia strain ATCC 39006 is also virulent in Caenorhabditis elegans (15) and potato tuber-rotting (17) infection models, demonstrating a broad-host-range capacity for pathogenesis in insect and plant hosts.The Pig biosynthetic pathway was recently elucidated and requires gene products from the pigA-pigO operon (24, 57), which is transcribed as a polycistronic mRNA (47). Considerable progress has been made in unraveling the complex regulatory network that governs the production of Pig in Serratia strain ATCC 39006. For example, an N-acyl homoserine lactone quorum-sensing system (55), encoded by the SmaIR locus, derepresses the transcription of the Pig biosynthetic genes in response to cell density by modula...

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Biosynthesis of prodigiosin. Incorporation patterns of carbon-13-labeled alanine, proline, glycine, and serine elucidated by Fourier transform nuclear magnetic resonance

Cited by 61 publications

References 0 publications

Biosynthesis of the red antibiotic, prodigiosin, in Serratia: identification of a novel 2‐methyl‐3‐n‐amyl‐pyrrole (MAP) assembly pathway, definition of the terminal condensing enzyme, and implications for undecylprodigiosin biosynthesis in Streptomyces

Biosynthesis of the red antibiotic, prodigiosin, in Serratia: identification of a novel 2‐methyl‐3‐n‐amyl‐pyrrole (MAP) assembly pathway, definition of the terminal condensing enzyme, and implications for undecylprodigiosin biosynthesis in Streptomyces

Viscosity dictates metabolic activity of Vibrio ruber

Virulence and Prodigiosin Antibiotic Biosynthesis inSerratiaAre Regulated Pleiotropically by the GGDEF/EAL Domain Protein, PigX

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