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      A brief review of bioluminescent systems (2019)

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          Abstract

          Despite being widely used in reporter technologies, bioluminescent systems are largely understudied. Of at least forty different bioluminescent systems thought to exist in nature, molecular components of only seven light-emitting reactions are known, and the full biochemical pathway leading to light emission is only understood for two of them. Here, we provide a succinct overview of currently known bioluminescent systems highlighting available tools for research and discussing future applications.

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          Most cited references56

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          Codon-optimized Gaussia luciferase cDNA for mammalian gene expression in culture and in vivo.

          Photoproteins have played a major role in advancing our understanding of biological processes. A broader array of biocompatible, nontoxic, and novel reporters can serve to expand this potential. Here we describe the properties of a luciferase from the copepod marine organism Gaussia princeps. It is a monomeric protein composed of 185 aa (19.9 kDa) with a short coding sequence (555 bp) making it suitable for viral vectors. The humanized form of Gaussia luciferase (hGLuc) was efficiently expressed in mammalian cells following delivery by HSV-1 amplicon vectors. It was found to be nontoxic and naturally secreted, with flash bioluminescence characteristics similar to those of other coelenterazine luciferases. hGLuc generated over 1000-fold higher bioluminescent signal intensity from live cells together with their immediate environment and over 100-fold higher intensity from viable cells alone (not including secreted luciferase) or cell lysates, compared to humanized forms of firefly (hFLuc) and Renilla (hRLuc) luciferases expressed under similar conditions. Furthermore, hGLuc showed 200-fold higher signal intensity than hRLuc and intensity comparable to that of hFLuc in vivo under standard imaging conditions. Gaussia luciferase provides a sensitive means of imaging gene delivery and other events in living cells in culture and in vivo, with a unique combination of features including high signal intensity, secretion, and ATP independence, thus being able to report from the cells and their environment in real time.
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            1001 lights: luciferins, luciferases, their mechanisms of action and applications in chemical analysis, biology and medicine.

            Bioluminescence (BL) is a spectacular phenomenon involving light emission by live organisms. It is caused by the oxidation of a small organic molecule, luciferin, with molecular oxygen, which is catalysed by the enzyme luciferase. In nature, there are approximately 30 different BL systems, of which only 9 have been studied to various degrees in terms of their reaction mechanisms. A vast range of in vitro and in vivo analytical techniques have been developed based on BL, including tests for different analytes, immunoassays, gene expression assays, drug screening, bioimaging of live organisms, cancer studies, the investigation of infectious diseases and environmental monitoring. This review aims to cover the major existing applications for bioluminescence in the context of the diversity of luciferases and their substrates, luciferins. Particularly, the properties and applications of d-luciferin, coelenterazine, bacterial, Cypridina and dinoflagellate luciferins and their analogues along with their corresponding luciferases are described. Finally, four other rarely studied bioluminescent systems (those of limpet Latia, earthworms Diplocardia and Fridericia and higher fungi), which are promising for future use, are also discussed.
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              Monitoring bioluminescent Staphylococcus aureus infections in living mice using a novel luxABCDE construct.

              Strains of Staphylococcus aureus were transformed with plasmid DNA containing a Photorhabdus luminescens lux operon (luxABCDE) that was genetically modified to be functional in both gram-positive and gram-negative bacteria. S. aureus cells containing this novel lux construct, downstream of an appropriate promoter sequence, are highly bioluminescent, allowing the detection of fewer than 100 CFU in vitro (direct detection of exponentially dividing cells in liquid culture). Furthermore, these bacteria produce light stably at 37 degrees C and do not require exogenous aldehyde substrate, thus allowing S. aureus infections in living animals to be monitored by bioluminescence. Two strains of S. aureus 8325-4 that produce high levels of constitutive bioluminescence were injected into the thigh muscles of mice, and the animals were then either treated with the antibiotic amoxicillin or left untreated. Bioluminescence from bacteria present in the thighs of the mice was monitored in vivo over a period of 24 h. The effectiveness of the antibiotic in the treated animals could be measured by a decrease in the light signal. At 8 h, the infection in both groups of treated animals had begun to clear, as judged by a decrease in bioluminescence, and by 24 h no light signal could be detected. In contrast, both groups of untreated mice had strong bioluminescent signals at 24 h. Quantification of CFU from bacteria extracted from the thigh muscles of the mice correlated well with the bioluminescence data. This paper shows for the first time that bioluminescence offers a method for monitoring S. aureus infections in vivo that is sensitive and noninvasive and requires fewer animals than conventional methodologies.
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                Author and article information

                Contributors
                karen.s.sarkisyan@gmail.com
                Journal
                Curr Genet
                Curr. Genet
                Current Genetics
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0172-8083
                1432-0983
                8 March 2019
                8 March 2019
                2019
                : 65
                : 4
                : 877-882
                Affiliations
                [1 ]ISNI 0000000122478951, GRID grid.14105.31, Synthetic Biology Group, , MRC London Institute of Medical Sciences, ; London, UK
                [2 ]ISNI 0000 0001 2113 8111, GRID grid.7445.2, Institute of Clinical Sciences, Faculty of Medicine, , Imperial College London, ; London, UK
                [3 ]Planta LLC, Bolshoi Boulevard, 42 Str 1, Office 335, Moscow, 121205 Russia
                [4 ]ISNI 0000 0004 0440 1573, GRID grid.418853.3, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, ; Miklukho-Maklaya, 16/10, Moscow, 117997 Russia
                Author notes

                Communicated by M. Kupiec.

                Author information
                http://orcid.org/0000-0002-5375-6341
                Article
                951
                10.1007/s00294-019-00951-5
                6620254
                30850867
                6782c73a-7eb5-45ad-b527-c008259350bf
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 13 February 2019
                : 27 February 2019
                : 1 March 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100006769, Russian Science Foundation;
                Award ID: 17-74-10066
                Award Recipient :
                Categories
                Mini-Review
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2019

                Genetics
                bioluminescence,luciferin,luciferase,synthetic biology,imaging
                Genetics
                bioluminescence, luciferin, luciferase, synthetic biology, imaging

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