Antimicrobial activity of non-natural prodigiosenes

Marchal, Estelle; Uddin, Imam; Smithen, Deborah A.; Hawco, Cassandra L.A.; Lanteigne, Martin; Overy, David P.; Kerr, Russell G.; Thompson, Alison

doi:10.1039/c3ra45479g

Cited by 28 publications

(29 citation statements)

References 43 publications

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“…Antimicrobial and cytotoxic activity : Several mechanisms for cytotoxicity and antibiotic activity against various Gram‐negative and Gram‐positive bacteria have already been reported for prodiginines in refs. , , and . Therefore, a high tolerance towards these toxic compounds is essential for a heterologous mutasynthetic approach.…”

Section: Resultsmentioning

confidence: 99%

Preparation of Cyclic Prodiginines by Mutasynthesis in Pseudomonas putida KT2440

et al. 2018

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Prodiginines are a group of naturally occurring pyrrole alkaloids produced by various microorganisms and known for their broad biological activities. The production of nature-inspired cyclic prodiginines was enabled by combining organic synthesis with a mutasynthesis approach based on the GRAS (generally recognized as safe) certified host strain Pseudomonas putida KT2440. The newly prepared prodiginines exerted antimicrobial effects against relevant alternative biotechnological microbial hosts whereas P. putida itself exhibited remarkable tolerance against all tested prodiginines, thus corroborating the bacterium's exceptional suitability as a mutasynthesis host for the production of these cytotoxic secondary metabolites. Moreover, the produced cyclic prodiginines proved to be autophagy modulators in human breast cancer cells. One promising cyclic prodiginine derivative stood out, being twice as potent as prodigiosin, the most prominent member of the prodiginine family, and its synthetic derivative obatoclax mesylate.

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Section: Resultsmentioning

confidence: 99%

Preparation of Cyclic Prodiginines by Mutasynthesis in Pseudomonas putida KT2440

et al. 2018

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“…It was found to have a broad spectrum of activity against a wide range of Gram-positive and Gram-negative bacteria [5]. This natural product has attracted widespread attention in the medicinal chemistry field because of its wide range of biological activities, including antimicrobial activity [5], anti-malaria activity [6,7], immunosuppressive activity [4,9,10], and antitumor activity [11][12][13]. Here, it was completely synthesized [4].…”

Section: Discussionmentioning

confidence: 99%

“…The A and B pyrrole rings are directly connected, while the third ring is connected by a methyl bridge [3,4]. These components are synthesized by Gram-positive bacteria and Gram-negative bacteria, such as Pseudomonas, Vibrio, Streptomyces and Serratia, that have antimicrobial activity [5], anti-malarial activity [6,7], immunosuppressive activity [8][9][10], and antitumor activity [11][12][13]. Serratamolide was isolated for the first time in 1961 [14] from a Serratia marcescens.…”

Section: Introductionmentioning

confidence: 99%

Antibacterial Activity of a Novel Depsipeptide and Prodigiosine of Serratia marcescans S823

Zhu¹,

Pang²,

Chen³

et al. 2018

Nat Prod Chem Res

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To investigate the antimicrobial activity of secondary metabolites from Serratia marcescans S823. The strain Serratia marcescans S823 was screened for its antibacterial activity. The active components from the bacterium were isolated by bioactivity-guided analysis. Their structures were identified by chemical and spectroscopic methods to be prodigiosine (PG) (1), serratamolide A (2) and serratamolide G (3), which is a new compound. The MIC and MBC of prodigiosine and serratamolide G were 6.25 μg.mL-1 and 12.5 μg.mL-1 against C. albicans and 6.25 μg.mL-1 and 25 μg.mL-1 against B. thuringiensis respectively. They might be potential alternative treatment options for Candida albicans infection. This study encourages further investigation of natural products as new antibiotics.

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“…Compounds in both families possess a bipyrrole core that interacts with biologically relevant ions, from which most of their bioactive properties emerge . The structural variation found in members of these families, such as macrocyclization and halogenation, alters the potency and specificity of their bioactivities . For this reason many studies have concentrated on chemical synthesis of analogues; however, the native bacterial producers have already evolved a simple biosynthetic mechanism to allow for straightforward generation of structural diversity …”

Section: Introductionmentioning

confidence: 99%

Purification and Kinetic Characterization of the Essential Condensation Enzymes Involved in Prodiginine and Tambjamine Biosynthesis

et al. 2019

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Prodiginines and tambjamines are related families of bioactive alkaloid natural products with pharmaceutical potential. Both compound families result from a convergent biosynthetic pathway ending in the condensation of a conserved bipyrrole core with a variable partner. This reaction is performed by unique condensation enzymes, and has the potential to be manipulated to produce new pyrrolic compounds. We have purified and reconstituted the in vitro activity of the condensation enzymes PigC and TamQ from Pseudoalteromonas sp., which are involved, respectively, in the prodiginine and tambjamine biosynthetic pathways. Kinetic analysis confirmed a Uni Uni Bi Uni ping‐pong reaction sequence with competitive and uncompetitive substrate inhibition for PigC and TamQ respectively. The kinetic parameters of each enzyme provide insight into their differing substrate scope, and suggest that TamQ may have evolved a wide substrate tolerance that can be used for the production of novel prodiginines and tambjamines.

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Antimicrobial activity of non-natural prodigiosenes

Cited by 28 publications

References 43 publications

Preparation of Cyclic Prodiginines by Mutasynthesis in Pseudomonas putida KT2440

Preparation of Cyclic Prodiginines by Mutasynthesis in Pseudomonas putida KT2440

Antibacterial Activity of a Novel Depsipeptide and Prodigiosine of Serratia marcescans S823

Purification and Kinetic Characterization of the Essential Condensation Enzymes Involved in Prodiginine and Tambjamine Biosynthesis

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