Evolutionary dynamics of membrane transporters and channels: enhancing function through fusion

Willson, Benjamin J.; Chapman, Liam; Thomas, Gavin H.

doi:10.1016/j.gde.2019.07.017

Cited by 10 publications

(12 citation statements)

References 98 publications

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“…Our discovery of protein fusions between the sialic acid mutarotase, NanM, and two unrelated types of sialic acid transporters (ST4 and ST5) is the first ever report of a covalent coupling between a metabolic enzyme and a transporter in sialic acid biology. It is intriguing that, in both of these independent instances of fusion, the fusion takes place at the N-terminus of the transporter, rather than at the C-terminus where is most frequent in bacteria [84, 85]; however, the extracytoplasmic positioning of the NanM moiety makes mechanistic sense and can be understood thinking of the location of NanM as a periplasmic enzyme. The biological function of NanM in the periplasm has been proposed to be to help bacteria acquire more rapidly the transported anomer of Neu5Ac, which is the beta-anomer [66] (Fig.…”

Section: Discussionmentioning

confidence: 99%

Multiple evolutionary origins reflect the importance of sialic acid transporters in the colonisation potential of bacterial pathogens and commensals

Severi

Rudden

Bell

et al. 2021

Preprint

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Located at the tip of cell surface glycoconjugates, sialic acids are at the forefront of host-microbe interactions and, being easily liberated by sialidase enzymes, are used as metabolites by numerous bacteria, particularly by pathogens and commensals living on or near diverse mucosal surfaces. These bacteria rely on specific transporters for the acquisition of host-derived sialic acids. Here, we present the first comprehensive genomic and phylogenetic analysis of bacterial sialic acid transporters, leading to the identification of multiple new families and subfamilies. Our phylogenetic analysis suggests that sialic acid-specific transport has evolved independently at least 8 times during the evolution of bacteria, from within 4 of the major families/superfamilies of bacterial transporters, and we propose a robust classification scheme to bring together a myriad of different nomenclatures that exist to date. The new transporters discovered occur in diverse bacteria including Spirochaetes, Bacteroidetes, Planctomycetes, and Verrucomicrobia, many of which are species that have not been previously recognised to have sialometabolic capacities. Two subfamilies of transporters stand out in being fused to the sialic acid mutarotase enzyme, NanM, and these transporter fusions are enriched in bacteria present in gut microbial communities. We also provide evidence for a possible function of a sialic acid transporter component in chemotaxis that is independent of transport. Our analysis supports the increasing experimental evidence that competition for host-derived sialic acid is a key phenotype for successful colonisation of complex mucosal microbiomes, such that a strong evolutionary selection has occurred for the emergence of sialic acid specificity within existing transporter architectures.

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Section: Discussionmentioning

confidence: 99%

Multiple evolutionary origins reflect the importance of sialic acid transporters in the colonisation potential of bacterial pathogens and commensals

Severi

Rudden

Bell

et al. 2021

Preprint

Self Cite

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“…In some cases, the fusion of certain regulators with the membrane transporter was observed which modifies the transporter efficiency in high temperatures and is responsible for the transport of metabolites. 173…”

Section: Engineering Efflux Transport Proteinsmentioning

confidence: 99%

“… However, it is noteworthy that every single part or protein of the complex tripartite system is important for the function of the transport mechanism. In some cases, the fusion of certain regulators with the membrane transporter was observed which modifies the transporter efficiency in high temperatures and is responsible for the transport of metabolites …”

Section: Engineering Efflux Transport Proteinsmentioning

confidence: 99%

Efflux Transporters’ Engineering and Their Application in Microbial Production of Heterologous Metabolites

et al. 2021

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Metabolic engineering of microbial hosts for the production of heterologous metabolites and biochemicals is an enabling technology to generate meaningful quantities of desired products that may be otherwise difficult to produce by traditional means. Heterologous metabolite production can be restricted by the accumulation of toxic products within the cell. Efflux transport proteins (transporters) provide a potential solution to facilitate the export of these products, mitigate toxic effects, and enhance production. Recent investigations using knockout lines, heterologous expression, and expression profiling of transporters have revealed candidates that can enhance the export of heterologous metabolites from microbial cell systems. Transporter engineering efforts have revealed that some exhibit flexible substrate specificity and may have broader application potentials. In this Review, the major superfamilies of efflux transporters, their mechanistic modes of action, selection of appropriate efflux transporters for desired compounds, and potential transporter engineering strategies are described for potential applications in enhancing engineered microbial metabolite production. Future studies in substrate recognition, heterologous expression, and combinatorial engineering of efflux transporters will assist efforts to enhance heterologous metabolite production in microbial hosts.

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“…These fusions were designed according to the structure and substrate‐specificity of the target transporters. [ 83 ] For example, the fusion of aquaglyceroporin responsible for an arsenite efflux with a C‐terminal arsenate reductase domain required for arsenite formation, had higher transport efficiency as the export process was directly coupled with the synthesis process in a whole‐cell microbial system. [ 84 ] Likewise, this strategy was also used for the fusion of importer with substrate‐consuming enzyme.…”

Section: Transporter Engineering In Microbial Cellsmentioning

confidence: 99%

“…Also, transporter fusions with certain regulation domains were designed to modify the transporter activity during substrate binding, enhance transporter performance under high temperatures, and so on. [ 83 ]…”

Section: Transporter Engineering In Microbial Cellsmentioning

confidence: 99%

Transporter Engineering for Microbial Manufacturing

Zhu

Zhou

Wang

et al. 2020

Biotechnology Journal

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Microbes play an important role in biotransformation and biosynthesis of biofuels, natural products, and polymers. Therefore, microbial manufacturing has been widely used in medicine, industry, and agriculture. However, common strategies including enzyme engineering, pathway optimization, and host engineering are generally inadequate to obtain an efficient microbial production system. Transporter engineering provides an alternative strategy to promote the transmembrane transfer of substrates, intermediates, and final products in microbial cells and thus enhances production by alleviating feedback inhibition and cytotoxicity caused by final products. According to the current studies in transport engineering, native transporters usually have low expression and poor transportation ability, resulting in inefficient transport processes and microbial production. In this review, current approaches for transporter mining, characterization, and verification are comprehensively summarized. Practical approaches to enhance the transport system in engineered cells, such as balancing transporter overexpression and cell growth, and evolution of native transporters are discussed. Furthermore, the applications of transporter engineering in microbial manufacturing, including enhancement of substrate utilization, concentration of metabolic flux to the target pathway, and acceleration of efflux and recovery of products, demonstrate its outstanding advantages and promising prospects.

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Evolutionary dynamics of membrane transporters and channels: enhancing function through fusion

Cited by 10 publications

References 98 publications

Multiple evolutionary origins reflect the importance of sialic acid transporters in the colonisation potential of bacterial pathogens and commensals

Multiple evolutionary origins reflect the importance of sialic acid transporters in the colonisation potential of bacterial pathogens and commensals

Efflux Transporters’ Engineering and Their Application in Microbial Production of Heterologous Metabolites

Transporter Engineering for Microbial Manufacturing

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