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

Picott, Katherine J.; Deichert, Julie A.; deKemp, Ella M.; Snieckus, Victor; Ross, Avena C.

doi:10.1002/cbic.201900503

Cited by 10 publications

(9 citation statements)

References 38 publications

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“…The pathway requires as many as 14 genes; 12 encode for proteins directly involved in the biochemical synthesis of prodigiosin while the remaining 2 are thought to have auxiliary roles (Loeschcke et al, 2013). The pathway is bifurcated in which the final step, the condensation of 4-methoxy-2,2′-bipyrrole-5-carbaldehyde and monopyrrole (MBC) and 2-methyl-3-namyl-pyrrole (MAP), is catalysed by pigC (Picott et al, 2020). Prodiogiosin is synthesized in several species of bacteria (Darshan and Manonmani, 2015).…”

Section: Discussionmentioning

confidence: 99%

Native Production of Prodigiosin in the Estuarine Bacterium, Vibrio gazogenes PB1, and Identification of the Associated pig Genes

et al. 2022

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Vibrio gazogenes PB1 is an estuarine bacterium that was first isolated from saltwater mud. This bacterial species possesses the metabolic capacity to produce prodigiosin which has potential uses as an anticancer agent, antibiotic, and a fungicide. We evaluated the feasibility of employing V. gazogenes PB1 as a bacterial host for the production of prodigiosin. V. gazogenes PB1 could be grown and maintained using the well-known lysogeny broth medium when supplemented with NaCl, and revived after storage at -80°C. Under batch conditions, growth of V. gazogenes PB1 in minimal media and production of prodigiosin was observed over a wide range of NaCl concentrations from 1 to 5% (w/v). The production of prodigiosin was significantly influenced by the concentration of glucose (as the carbon source), ammonium chloride (as the nitrogen source), inorganic phosphate ions, as well as pH. The greatest titer (231 mg/L) was observed in minimal media that contained 1% (w/v) glucose, 100 mM ammonium chloride and 100 mM potassium phosphate buffer. The sequences and chromosomal locations of the pig genes associated with prodigiosin biosynthesis are revealed for the first time. PigA is an isolated gene on chromosome 2, while the remaining pig genes, from pigB to pigN, exist as a 20 kb gene cluster on chromosome 1. Given its excellent growth in a range of NaCl concentrations, wide availability from culture collections and low-risk status for experimental work, we would conclude that V. gazogenes PB1 is a promising bacterial host for the production of prodigiosin.

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Section: Discussionmentioning

confidence: 99%

Native Production of Prodigiosin in the Estuarine Bacterium, Vibrio gazogenes PB1, and Identification of the Associated pig Genes

et al. 2022

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“…Other talks described the elucidation and chemical logic of biosynthetic pathways leading to the C-nucleoside formycin A (Nigel Richards) [34], and nemamides, which are novel hybrid polykeptide/non-ribosomal peptide natural products (Rebecca Butcher) [35]. Continuing this theme, Avena Ross outlined how she is employing genome analysis to identify and understand the evolutionary history of pathways leading to naturally occurring poly-pyrroles such as the tambjamines (figure 3) [36].…”

Section: Other Topicsmentioning

confidence: 99%

Reactivity and mechanism in chemical and synthetic biology

Richards

Bearne

Parker

2023

Phil. Trans. R. Soc. B

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Physical organic chemistry and mechanistic thinking provide a strong intellectual framework for understanding the chemical logic of evolvable informational macromolecules and metabolic transformations in living organisms. These concepts have also led to numerous successes in designing and applying tools to delineate biological function in health and disease, chemical ecology and possible alternative chemistries employed by extraterrestrial life. A symposium at the 2020 Pacifichem meeting was scheduled in December 2020 to discuss designing and exploiting expanded genetic alphabets, methods to understand the biosynthesis of natural products and re-engineering primary metabolism in bacteria. The COVID-19 pandemic led to postponement of in-person discussions, with the symposium eventually being held on 20–21 December 2021 as an online event. This issue is a written record of work presented on biosynthetic pathways and enzyme catalysis, engineering microorganisms with new metabolic capabilities, and the synthesis of non-canonical, nucleobases for medical applications and for studies of alternate chemistries for living organisms. The variety of opinion pieces, reviews and original research articles provide a starting point for innovations that clarify how complex biological systems emerge from the rules of chemical reactivity and mechanism. This article is part of the themed issue ‘Reactivity and mechanism in chemical and synthetic biology’.

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“…17,18 This NP contains a tripyrrolic structure that is ultimately assembled by the PigC-catalyzed condensation of 4-methoxy-2,2ʹ-bipyrrole-5carboxaldehyde (MBC) and methylamylpyrrole (MAP) ( Figure S1). 19,20 A considerable number of naturally occurring analogues of this tripyrrole NP exist including the Streptomyces coelicolor metabolites undecylprodigiosin (2, Figure 2) and streptorubin B (3, Figure S2). 21,22 A second group of bipyrrolic analogues are the tambjamines exemplified by tambjamine YP1 (4, Figure 2) from Pseudoalteromonas tunicata and produced predominantly by marine microorganisms.…”

Section: Introductionmentioning

confidence: 99%

Identification of a Tambjamine Gene Cluster in Streptomyces Reveals Convergent Evolution of the Biosynthetic Pathway

Grenade¹,

Chiriac²,

Howe³

et al. 2020

Preprint

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Bacterial natural products are an immensely valuable source of therapeutics. As modern DNA sequencing efforts provide increasing numbers of microbial genomes, it is clear that the molecules produced by most natural product biosynthetic gene clusters (BGCs) remain unknown. Genome mining makes use of bioinformatic techniques to elucidate the natural products produced by these “orphan” BGCs. Here, we report the use of sequence similarity networks (SSNs) and genome neighborhood networks (GNNs) to identify an orphan BGC that is responsible for the production of the antitumor tambjamine BE-18591 in Streptomyces albus NRRL B-2362. Although BE-18591 is a close structural analogue of tambjamine YP1 produced by Pseudoalteromonas tunicata, the biosynthetic routes to produce these molecules differ significantly. Notably, the C12-alkylamine tail that is appended onto the bipyrrole core of tambjamine YP1 is derived from fatty acids siphoned from the primary metabolism of the pseudoalteromonad, whilst the S. albus NRRL B-2362 BGC encodes a dedicated system for the de novo biosynthesis of the alkylamine portion of tambjamine BE-18591. These remarkably different biosynthetic strategies represent a striking example of convergent BGC evolution, with selective pressure for the production of tambjamines seemingly leading to the emergence of separate biosynthetic pathways in pseudoalteromonads and streptomycetes that ultimately produce closely related compounds

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

Cited by 10 publications

References 38 publications

Native Production of Prodigiosin in the Estuarine Bacterium, Vibrio gazogenes PB1, and Identification of the Associated pig Genes

Native Production of Prodigiosin in the Estuarine Bacterium, Vibrio gazogenes PB1, and Identification of the Associated pig Genes

Reactivity and mechanism in chemical and synthetic biology

Identification of a Tambjamine Gene Cluster in Streptomyces Reveals Convergent Evolution of the Biosynthetic Pathway

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