TransportDB 2.0: a database for exploring membrane transporters in sequenced genomes from all domains of life

Elbourne, Liam D. H.; Tetu, Sasha G.; Hassan, Karl A.; Paulsen, Ian T.

doi:10.1093/nar/gkw1068

Cited by 259 publications

(229 citation statements)

References 21 publications

(26 reference statements)

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“…Transport protein predictions were made using the Transporter Automated Annotation Pipeline (TransAAP [53]) to identify putative Zn and Cu transporters. Where orthologous/paralogous efflux transporters were identified between/within strains, genetic maps demonstrating the conservation of their coding gene and surrounding genes were generated using the Easyfig tool [54].…”

Section: Methodsmentioning

confidence: 99%

Zinc stress induces copper depletion in Acinetobacter baumannii

et al. 2017

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BackgroundThe first row transition metal ions zinc and copper are essential to the survival of many organisms, although in excess these ions are associated with significant toxicity. Here, we examined the impact of zinc and copper stress on Acinetobacter baumannii, a common opportunistic pathogen.ResultsWe show that extracellular zinc stress induces a copper-specific depletion phenotype in A. baumannii ATCC 17978. Supplementation with copper not only fails to rescue this phenotype, but further exacerbates the copper depletion. Extensive analysis of the A. baumannii ATCC 17978 genome identified 13 putative zinc/copper resistance efflux pumps. Transcriptional analyses show that four of these transporters are responsive to zinc stress, five to copper stress and seven to the combination of zinc and copper stress, thereby revealing a likely foundation for the zinc-induced copper starvation in A. baumannii. In addition, we show that zinc and copper play crucial roles in management of oxidative stress and the membrane composition of A. baumannii. Further, we reveal that zinc and copper play distinct roles in macrophage-mediated killing of this pathogen.ConclusionsCollectively, this study supports the targeting of metal ion homeostatic mechanisms as an effective antimicrobial strategy against multi-drug resistant bacterial pathogens.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-017-0965-y) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Zinc stress induces copper depletion in Acinetobacter baumannii

et al. 2017

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“…The latest version of transportDB [64] http://www.membranetransport.org/transportDB2/overview.html, the most comprehensive listing, gives 341 transporters for S. cerevisiae S288c, and shows that improvements in identification have been less than substantial. In general, the efflux transporters seem to have evolved to remove natural toxins from the yeast's environment [65,66], are highly promiscuous [67,68], and many are known as pleiotropic drug transporters (PDRs) [69].…”

Section: A Large Percentage Of Orphans Even In Well-studied Organismsmentioning

confidence: 99%

Control of metabolite efflux in microbial cell factories: current advances and future prospects

Kell¹

2018

Preprint

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The yield and ease of purification of biotechnological products are typically greatly enhanced if they can be secreted into the external medium. Although not universally appreciated, however, small molecule biotechnological products do not ‘float across’ the phospholipid bilayer portion of biological membranes, and thus they need transporters to assist their passage into the extramembrane and extracellular spaces. Some of these transporters may be reversible, equilibrative transporters that might more normally be used for uptake, while others may have an efflux directionality imposed on them via suitable energy coupling mechanisms. Despite the energetic costs of small molecule synthesis, natural evolution does in fact provide a number of mechanisms by which the secretion of such products can actually enhance fitness. Where available these provide useful starting points, and assaying for such activities is crucial. In particular, in a systems biology approach, we first need to identify such/suitable activities before we can seek to increase them. They may then be improved through promoter engineering, via manipulation of control elements, or by directed evolution of the transporter proteins themselves. Modern methods of synthetic biology provide enormous opportunities for all kinds of efflux transporter engineering; they are just beginning to be realised.

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“…The genome-scale metabolic network reconstruction for K. marxianus DMKU3-1042 was based on published genome annotation (NCBI accession PRJDA65233) and other databases including KEGG [14], MetaCyc [15], TransportDB [16] and BRENDA [17]. Two draft models were generated using the RAVEN Toolbox [18].…”

Section: Model Reconstructionmentioning

confidence: 99%

“…The draft model was then thoroughly curated for gene associations, EC numbers, metabolite names, reactions elemental/charge balance. Here we considered Yeast 7.6 [22], BRENDA [17] and MetaCyc [15], TransportDB [16] as reference. The additional information for every reaction is included in Additional file 2 (the list of reactions, followed by the column which state from in which step it was added).…”

Section: Manual Curationmentioning

confidence: 99%

Reconstruction and Analysis of aKluyveromyces marxianusGenome-scale Metabolic Model

Marcišauskas¹,

Ji²,

Nielsen³

2019

Preprint

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Background: Kluyveromyces marxianus is a thermotolerant yeast with multiple biotechnological potentials for industrial applications, which can metabolize a broad range of carbon sources, including less conventional sugars like lactose, xylose, arabinose and inulin. These phenotypic traits are sustained even up to 45°C, what makes it a relevant candidate for industrial biotechnology applications, such as ethanol production. It is therefore of much interest to get more insight into the metabolism of this yeast. Recent studies suggested, that thermotolerance is achieved by reducing the number of growth-determining proteins or suppressing oxidative phosphorylation. Here we aimed to find related factors contributing to the thermotolerance of K. marxianus.Results: Here, we reported the first genome-scale metabolic model of Kluyveromyces marxianus, iSM996, using a publicly available Kluyveromyces lactis model as template. The model was manually curated and refined to include missing species-specific metabolic capabilities. The iSM996 model includes 1913 reactions, associated with 996 genes and 1531 metabolites. It performed well to predict the carbon source utilization and growth rates under different growth conditions. Moreover, the model was coupled with transcriptomics data and used to perform simulations at various growth temperatures.Conclusions: K. marxianus iSM996 represents a well-annotated metabolic model of thermotolerant yeast, which provide new insight into theoretical metabolic profiles at different temperatures of K. marxianus. This could accelerate the integrative analysis of multi-omics data, leading to model-driven strain design and improvement.

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TransportDB 2.0: a database for exploring membrane transporters in sequenced genomes from all domains of life

Cited by 259 publications

References 21 publications

Zinc stress induces copper depletion in Acinetobacter baumannii

Zinc stress induces copper depletion in Acinetobacter baumannii

Control of metabolite efflux in microbial cell factories: current advances and future prospects

Reconstruction and Analysis of aKluyveromyces marxianusGenome-scale Metabolic Model

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