[{"publication_status":"published","publication_identifier":{"issn":["2050-084X"]},"file_date_updated":"2022-06-20T07:44:19Z","abstract":[{"text":"Studies of protein fitness landscapes reveal biophysical constraints guiding protein evolution and empower prediction of functional proteins. However, generalisation of these findings is limited due to scarceness of systematic data on fitness landscapes of proteins with a defined evolutionary relationship. We characterized the fitness peaks of four orthologous fluorescent proteins with a broad range of sequence divergence. While two of the four studied fitness peaks were sharp, the other two were considerably flatter, being almost entirely free of epistatic interactions. Mutationally robust proteins, characterized by a flat fitness peak, were not optimal templates for machine-learning-driven protein design – instead, predictions were more accurate for fragile proteins with epistatic landscapes. Our work paves insights for practical application of fitness landscape heterogeneity in protein engineering.","lang":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"intvolume":"        11","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"}],"has_accepted_license":"1","article_type":"original","date_created":"2022-06-18T09:06:59Z","volume":11,"oa_version":"Published Version","title":"Heterogeneity of the GFP fitness landscape and data-driven protein design","author":[{"id":"4720D23C-F248-11E8-B48F-1D18A9856A87","full_name":"Gonzalez Somermeyer, Louisa","last_name":"Gonzalez Somermeyer","orcid":"0000-0001-9139-5383","first_name":"Louisa"},{"last_name":"Fleiss","full_name":"Fleiss, Aubin","first_name":"Aubin"},{"first_name":"Alexander S","full_name":"Mishin, Alexander S","last_name":"Mishin"},{"last_name":"Bozhanova","full_name":"Bozhanova, Nina G","first_name":"Nina G"},{"last_name":"Igolkina","full_name":"Igolkina, Anna A","first_name":"Anna A"},{"full_name":"Meiler, Jens","last_name":"Meiler","first_name":"Jens"},{"full_name":"Alaball Pujol, Maria-Elisenda","last_name":"Alaball Pujol","first_name":"Maria-Elisenda"},{"last_name":"Putintseva","full_name":"Putintseva, Ekaterina V","first_name":"Ekaterina V"},{"first_name":"Karen S","full_name":"Sarkisyan, Karen S","last_name":"Sarkisyan"},{"last_name":"Kondrashov","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","full_name":"Kondrashov, Fyodor","orcid":"0000-0001-8243-4694","first_name":"Fyodor"}],"day":"05","scopus_import":"1","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"ama":"Gonzalez Somermeyer L, Fleiss A, Mishin AS, et al. Heterogeneity of the GFP fitness landscape and data-driven protein design. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/elife.75842\">10.7554/elife.75842</a>","short":"L. Gonzalez Somermeyer, A. Fleiss, A.S. Mishin, N.G. Bozhanova, A.A. Igolkina, J. Meiler, M.-E. Alaball Pujol, E.V. Putintseva, K.S. Sarkisyan, F. Kondrashov, ELife 11 (2022).","ieee":"L. Gonzalez Somermeyer <i>et al.</i>, “Heterogeneity of the GFP fitness landscape and data-driven protein design,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","ista":"Gonzalez Somermeyer L, Fleiss A, Mishin AS, Bozhanova NG, Igolkina AA, Meiler J, Alaball Pujol M-E, Putintseva EV, Sarkisyan KS, Kondrashov F. 2022. Heterogeneity of the GFP fitness landscape and data-driven protein design. eLife. 11, 75842.","chicago":"Gonzalez Somermeyer, Louisa, Aubin Fleiss, Alexander S Mishin, Nina G Bozhanova, Anna A Igolkina, Jens Meiler, Maria-Elisenda Alaball Pujol, Ekaterina V Putintseva, Karen S Sarkisyan, and Fyodor Kondrashov. “Heterogeneity of the GFP Fitness Landscape and Data-Driven Protein Design.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/elife.75842\">https://doi.org/10.7554/elife.75842</a>.","mla":"Gonzalez Somermeyer, Louisa, et al. “Heterogeneity of the GFP Fitness Landscape and Data-Driven Protein Design.” <i>ELife</i>, vol. 11, 75842, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/elife.75842\">10.7554/elife.75842</a>.","apa":"Gonzalez Somermeyer, L., Fleiss, A., Mishin, A. S., Bozhanova, N. G., Igolkina, A. A., Meiler, J., … Kondrashov, F. (2022). Heterogeneity of the GFP fitness landscape and data-driven protein design. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.75842\">https://doi.org/10.7554/elife.75842</a>"},"language":[{"iso":"eng"}],"oa":1,"article_number":"75842","file":[{"relation":"main_file","checksum":"7573c28f44028ab0cc81faef30039e44","success":1,"file_name":"2022_eLife_Somermeyer.pdf","access_level":"open_access","content_type":"application/pdf","file_id":"11454","date_created":"2022-06-20T07:44:19Z","file_size":5297213,"date_updated":"2022-06-20T07:44:19Z","creator":"dernst"}],"department":[{"_id":"GradSch"},{"_id":"FyKo"}],"month":"05","quality_controlled":"1","ddc":["570"],"type":"journal_article","date_updated":"2023-08-03T07:20:15Z","_id":"11448","publisher":"eLife Sciences Publications","doi":"10.7554/elife.75842","article_processing_charge":"No","date_published":"2022-05-05T00:00:00Z","acknowledgement":"We thank Ondřej Draganov, Rodrigo Redondo, Bor Kavčič, Mia Juračić and Andrea Pauli for discussion and technical advice. We thank Anita Testa Salmazo for advice on resin protein purification, Dmitry Bolotin and the Milaboratory (milaboratory.com) for access to computing and storage infrastructure, and Josef Houser and Eva Fujdiarova for technical assistance and data interpretation. Core facility Biomolecular Interactions and Crystallization of CEITEC Masaryk University is gratefully acknowledged for the obtaining of the scientific data presented in this paper. This research was supported by the Scientific Service Units (SSU) of IST-Austria\r\nthrough resources provided by the Bioimaging Facility (BIF), and the Life Science Facility (LSF). MiSeq and HiSeq NGS sequencing was performed by the Next Generation Sequencing Facility at Vienna BioCenter Core Facilities (VBCF), member of the Vienna BioCenter (VBC), Austria. FACS was performed at the BioOptics Facility of the Institute of Molecular Pathology (IMP), Austria. We also thank the Biomolecular Crystallography Facility in the Vanderbilt University Center for Structural Biology. We are grateful to Joel M Harp for help with X-ray data collection. This work was supported by the ERC Consolidator grant to FAK (771209—CharFL). KSS acknowledges support by President’s Grant МК–5405.2021.1.4, the Imperial College Research Fellowship and the MRC London Institute of Medical Sciences (UKRI MC-A658-5QEA0).\r\nAF is supported by the Marie Skłodowska-Curie Fellowship (H2020-MSCA-IF-2019, Grant Agreement No. 898203, Project acronym \"FLINDIP\"). Experiments were partially carried out using equipment provided by the Institute of Bioorganic Chemistry of the Russian Academy of Sciences Сore Facility (CKP IBCH). This work was supported by a Russian Science Foundation grant 19-74-10102.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 665,385.","ec_funded":1,"project":[{"_id":"26580278-B435-11E9-9278-68D0E5697425","grant_number":"771209","name":"Characterizing the fitness landscape on population and global scales","call_identifier":"H2020"},{"call_identifier":"H2020","grant_number":"665385","name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"}],"status":"public","publication":"eLife","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"external_id":{"isi":["000799197200001"]},"isi":1,"year":"2022"},{"page":"944-946","ddc":["570"],"quality_controlled":"1","article_processing_charge":"No","doi":"10.1038/s41587-020-0500-9","publisher":"Springer Nature","_id":"7889","date_updated":"2023-09-05T15:30:34Z","type":"journal_article","status":"public","publication":"Nature Biotechnology","project":[{"grant_number":"771209","name":"Characterizing the fitness landscape on population and global scales","call_identifier":"H2020","_id":"26580278-B435-11E9-9278-68D0E5697425"}],"ec_funded":1,"pmid":1,"acknowledgement":"This study was designed, performed and funded by Planta LLC. We thank K. Wood for assisting in manuscript development. Planta acknowledges support from the Skolkovo Innovation Centre. We thank D. Bolotin and the Milaboratory (milaboratory.com) for access to computing and storage infrastructure. We thank S. Shakhov for providing\r\nphotography equipment. The Synthetic Biology Group is funded by the MRC London Institute of Medical Sciences (UKRI MC-A658-5QEA0, K.S.S.). K.S.S. is supported by an Imperial College Research Fellowship. Experiments were partially carried out using equipment provided by the Institute of Bioorganic Chemistry of the Russian Academy\r\nof Sciences Сore Facility (CKP IBCH; supported by the Russian Ministry of Education and Science Grant RFMEFI62117X0018). The F.A.K. lab is supported by ERC grant agreement 771209—CharFL. This project received funding from the European Union’s Horizon 2020 Research and Innovation Programme under Marie Skłodowska-Curie\r\nGrant Agreement 665385. K.S.S. acknowledges support by President’s Grant 075-15-2019-411. Design and assembly of some of the plasmids was supported by Russian Science Foundation grant 19-74-10102. Imaging experiments were partially supported by Russian Science Foundation grant 17-14-01169p. LC-MS/MS analyses of extracts were\r\nsupported by Russian Science Foundation grant 16-14-00052p. Design and assembly of plasmids was partially supported by grant 075-15-2019-1789 from the Ministry of Science and Higher Education of the Russian Federation allocated to the Center for Precision Genome Editing and Genetic Technologies for Biomedicine. The authors\r\nwould like to acknowledge the work of Genomics Core Facility of the Skolkovo Institute of Science and Technology, which performed the sequencing and bioinformatic analysis.","date_published":"2020-04-27T00:00:00Z","year":"2020","isi":1,"related_material":{"link":[{"url":"https://doi.org/10.1038/s41587-020-0578-0","relation":"erratum"}]},"external_id":{"pmid":["32341562"],"isi":["000529298800003"]},"has_accepted_license":"1","abstract":[{"text":"Autoluminescent plants engineered to express a bacterial bioluminescence gene cluster in plastids have not been widely adopted because of low light output. We engineered tobacco plants with a fungal bioluminescence system that converts caffeic acid (present in all plants) into luciferin and report self-sustained luminescence that is visible to the naked eye. Our findings could underpin development of a suite of imaging tools for plants.","lang":"eng"}],"intvolume":"        38","file_date_updated":"2021-03-02T23:30:03Z","publication_status":"published","publication_identifier":{"issn":["1087-0156"],"eissn":["1546-1696"]},"day":"27","scopus_import":"1","author":[{"full_name":"Mitiouchkina, Tatiana","last_name":"Mitiouchkina","first_name":"Tatiana"},{"first_name":"Alexander S.","full_name":"Mishin, Alexander S.","last_name":"Mishin"},{"last_name":"Gonzalez Somermeyer","full_name":"Gonzalez Somermeyer, Louisa","id":"4720D23C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9139-5383","first_name":"Louisa"},{"first_name":"Nadezhda M.","last_name":"Markina","full_name":"Markina, Nadezhda M."},{"full_name":"Chepurnyh, Tatiana V.","last_name":"Chepurnyh","first_name":"Tatiana V."},{"full_name":"Guglya, Elena B.","last_name":"Guglya","first_name":"Elena B."},{"full_name":"Karataeva, Tatiana A.","last_name":"Karataeva","first_name":"Tatiana A."},{"first_name":"Kseniia A.","last_name":"Palkina","full_name":"Palkina, Kseniia A."},{"last_name":"Shakhova","full_name":"Shakhova, Ekaterina S.","first_name":"Ekaterina S."},{"first_name":"Liliia I.","last_name":"Fakhranurova","full_name":"Fakhranurova, Liliia I."},{"full_name":"Chekova, Sofia V.","last_name":"Chekova","first_name":"Sofia V."},{"full_name":"Tsarkova, Aleksandra S.","last_name":"Tsarkova","first_name":"Aleksandra S."},{"first_name":"Yaroslav V.","full_name":"Golubev, Yaroslav V.","last_name":"Golubev"},{"full_name":"Negrebetsky, Vadim V.","last_name":"Negrebetsky","first_name":"Vadim V."},{"first_name":"Sergey A.","full_name":"Dolgushin, Sergey A.","last_name":"Dolgushin"},{"full_name":"Shalaev, Pavel V.","last_name":"Shalaev","first_name":"Pavel V."},{"first_name":"Dmitry","last_name":"Shlykov","full_name":"Shlykov, Dmitry"},{"first_name":"Olesya A.","last_name":"Melnik","full_name":"Melnik, Olesya A."},{"first_name":"Victoria O.","last_name":"Shipunova","full_name":"Shipunova, Victoria O."},{"first_name":"Sergey M.","full_name":"Deyev, Sergey M.","last_name":"Deyev"},{"last_name":"Bubyrev","full_name":"Bubyrev, Andrey I.","first_name":"Andrey I."},{"first_name":"Alexander S.","full_name":"Pushin, Alexander S.","last_name":"Pushin"},{"last_name":"Choob","full_name":"Choob, Vladimir V.","first_name":"Vladimir V."},{"first_name":"Sergey V.","last_name":"Dolgov","full_name":"Dolgov, Sergey V."},{"last_name":"Kondrashov","full_name":"Kondrashov, Fyodor","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","first_name":"Fyodor","orcid":"0000-0001-8243-4694"},{"first_name":"Ilia V.","full_name":"Yampolsky, Ilia V.","last_name":"Yampolsky"},{"last_name":"Sarkisyan","full_name":"Sarkisyan, Karen S.","first_name":"Karen S."}],"oa_version":"Submitted Version","title":"Plants with genetically encoded autoluminescence","volume":38,"date_created":"2020-05-25T15:02:00Z","article_type":"original","oa":1,"language":[{"iso":"eng"}],"citation":{"ista":"Mitiouchkina T, Mishin AS, Gonzalez Somermeyer L, Markina NM, Chepurnyh TV, Guglya EB, Karataeva TA, Palkina KA, Shakhova ES, Fakhranurova LI, Chekova SV, Tsarkova AS, Golubev YV, Negrebetsky VV, Dolgushin SA, Shalaev PV, Shlykov D, Melnik OA, Shipunova VO, Deyev SM, Bubyrev AI, Pushin AS, Choob VV, Dolgov SV, Kondrashov F, Yampolsky IV, Sarkisyan KS. 2020. Plants with genetically encoded autoluminescence. Nature Biotechnology. 38, 944–946.","chicago":"Mitiouchkina, Tatiana, Alexander S. Mishin, Louisa Gonzalez Somermeyer, Nadezhda M. Markina, Tatiana V. Chepurnyh, Elena B. Guglya, Tatiana A. Karataeva, et al. “Plants with Genetically Encoded Autoluminescence.” <i>Nature Biotechnology</i>. Springer Nature, 2020. <a href=\"https://doi.org/10.1038/s41587-020-0500-9\">https://doi.org/10.1038/s41587-020-0500-9</a>.","apa":"Mitiouchkina, T., Mishin, A. S., Gonzalez Somermeyer, L., Markina, N. M., Chepurnyh, T. V., Guglya, E. B., … Sarkisyan, K. S. (2020). Plants with genetically encoded autoluminescence. <i>Nature Biotechnology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41587-020-0500-9\">https://doi.org/10.1038/s41587-020-0500-9</a>","mla":"Mitiouchkina, Tatiana, et al. “Plants with Genetically Encoded Autoluminescence.” <i>Nature Biotechnology</i>, vol. 38, Springer Nature, 2020, pp. 944–46, doi:<a href=\"https://doi.org/10.1038/s41587-020-0500-9\">10.1038/s41587-020-0500-9</a>.","ama":"Mitiouchkina T, Mishin AS, Gonzalez Somermeyer L, et al. Plants with genetically encoded autoluminescence. <i>Nature Biotechnology</i>. 2020;38:944-946. doi:<a href=\"https://doi.org/10.1038/s41587-020-0500-9\">10.1038/s41587-020-0500-9</a>","ieee":"T. Mitiouchkina <i>et al.</i>, “Plants with genetically encoded autoluminescence,” <i>Nature Biotechnology</i>, vol. 38. Springer Nature, pp. 944–946, 2020.","short":"T. Mitiouchkina, A.S. Mishin, L. Gonzalez Somermeyer, N.M. Markina, T.V. Chepurnyh, E.B. Guglya, T.A. Karataeva, K.A. Palkina, E.S. Shakhova, L.I. Fakhranurova, S.V. Chekova, A.S. Tsarkova, Y.V. Golubev, V.V. Negrebetsky, S.A. Dolgushin, P.V. Shalaev, D. Shlykov, O.A. Melnik, V.O. Shipunova, S.M. Deyev, A.I. Bubyrev, A.S. Pushin, V.V. Choob, S.V. Dolgov, F. Kondrashov, I.V. Yampolsky, K.S. Sarkisyan, Nature Biotechnology 38 (2020) 944–946."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","month":"04","department":[{"_id":"FyKo"}],"file":[{"file_id":"8316","date_updated":"2021-03-02T23:30:03Z","creator":"dernst","embargo":"2021-03-01","file_size":1180086,"date_created":"2020-08-28T08:57:07Z","checksum":"1b30467500ec6277229a875b06e196d0","relation":"main_file","content_type":"application/pdf","access_level":"open_access","file_name":"2020_NatureBiotech_Mitiouchkina.pdf"}]},{"date_created":"2018-12-23T22:59:18Z","volume":115,"oa_version":"Published Version","title":"Genetically encodable bioluminescent system from fungi","author":[{"full_name":"Kotlobay, Alexey A.","last_name":"Kotlobay","first_name":"Alexey A."},{"full_name":"Sarkisyan, Karen","id":"39A7BF80-F248-11E8-B48F-1D18A9856A87","last_name":"Sarkisyan","first_name":"Karen","orcid":"0000-0002-5375-6341"},{"first_name":"Yuliana A.","full_name":"Mokrushina, Yuliana A.","last_name":"Mokrushina"},{"full_name":"Marcet-Houben, Marina","last_name":"Marcet-Houben","first_name":"Marina"},{"last_name":"Serebrovskaya","full_name":"Serebrovskaya, Ekaterina O.","first_name":"Ekaterina O."},{"last_name":"Markina","full_name":"Markina, Nadezhda M.","first_name":"Nadezhda M."},{"full_name":"Gonzalez Somermeyer, Louisa","id":"4720D23C-F248-11E8-B48F-1D18A9856A87","last_name":"Gonzalez Somermeyer","first_name":"Louisa","orcid":"0000-0001-9139-5383"},{"full_name":"Gorokhovatsky, Andrey Y.","last_name":"Gorokhovatsky","first_name":"Andrey Y."},{"first_name":"Andrey","full_name":"Vvedensky, Andrey","last_name":"Vvedensky"},{"last_name":"Purtov","full_name":"Purtov, Konstantin V.","first_name":"Konstantin V."},{"last_name":"Petushkov","full_name":"Petushkov, Valentin N.","first_name":"Valentin N."},{"first_name":"Natalja S.","full_name":"Rodionova, Natalja S.","last_name":"Rodionova"},{"first_name":"Tatiana V.","last_name":"Chepurnyh","full_name":"Chepurnyh, Tatiana V."},{"first_name":"Liliia","last_name":"Fakhranurova","full_name":"Fakhranurova, Liliia"},{"last_name":"Guglya","full_name":"Guglya, Elena B.","first_name":"Elena B."},{"full_name":"Ziganshin, Rustam","last_name":"Ziganshin","first_name":"Rustam"},{"last_name":"Tsarkova","full_name":"Tsarkova, Aleksandra S.","first_name":"Aleksandra S."},{"full_name":"Kaskova, Zinaida M.","last_name":"Kaskova","first_name":"Zinaida M."},{"full_name":"Shender, Victoria","last_name":"Shender","first_name":"Victoria"},{"first_name":"Maxim","last_name":"Abakumov","full_name":"Abakumov, Maxim"},{"last_name":"Abakumova","full_name":"Abakumova, Tatiana O.","first_name":"Tatiana O."},{"last_name":"Povolotskaya","full_name":"Povolotskaya, Inna S.","first_name":"Inna S."},{"last_name":"Eroshkin","full_name":"Eroshkin, Fedor M.","first_name":"Fedor M."},{"last_name":"Zaraisky","full_name":"Zaraisky, Andrey G.","first_name":"Andrey G."},{"full_name":"Mishin, Alexander S.","last_name":"Mishin","first_name":"Alexander S."},{"full_name":"Dolgov, Sergey V.","last_name":"Dolgov","first_name":"Sergey V."},{"first_name":"Tatiana Y.","last_name":"Mitiouchkina","full_name":"Mitiouchkina, Tatiana Y."},{"last_name":"Kopantzev","full_name":"Kopantzev, Eugene P.","first_name":"Eugene P."},{"last_name":"Waldenmaier","full_name":"Waldenmaier, Hans E.","first_name":"Hans E."},{"first_name":"Anderson G.","full_name":"Oliveira, Anderson G.","last_name":"Oliveira"},{"first_name":"Yuichi","last_name":"Oba","full_name":"Oba, Yuichi"},{"first_name":"Ekaterina","last_name":"Barsova","full_name":"Barsova, Ekaterina"},{"last_name":"Bogdanova","full_name":"Bogdanova, Ekaterina A.","first_name":"Ekaterina A."},{"first_name":"Toni","last_name":"Gabaldón","full_name":"Gabaldón, Toni"},{"first_name":"Cassius V.","last_name":"Stevani","full_name":"Stevani, Cassius V."},{"full_name":"Lukyanov, Sergey","last_name":"Lukyanov","first_name":"Sergey"},{"last_name":"Smirnov","full_name":"Smirnov, Ivan V.","first_name":"Ivan V."},{"full_name":"Gitelson, Josef I.","last_name":"Gitelson","first_name":"Josef I."},{"id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","full_name":"Kondrashov, Fyodor","last_name":"Kondrashov","first_name":"Fyodor","orcid":"0000-0001-8243-4694"},{"first_name":"Ilia V.","last_name":"Yampolsky","full_name":"Yampolsky, Ilia V."}],"scopus_import":"1","day":"11","publication_identifier":{"issn":["00278424"]},"publication_status":"published","file_date_updated":"2020-07-14T12:47:11Z","tmp":{"image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)"},"intvolume":"       115","abstract":[{"lang":"eng","text":"Bioluminescence is found across the entire tree of life, conferring a spectacular set of visually oriented functions from attracting mates to scaring off predators. Half a dozen different luciferins, molecules that emit light when enzymatically oxidized, are known. However, just one biochemical pathway for luciferin biosynthesis has been described in full, which is found only in bacteria. Here, we report identification of the fungal luciferase and three other key enzymes that together form the biosynthetic cycle of the fungal luciferin from caffeic acid, a simple and widespread metabolite. Introduction of the identified genes into the genome of the yeast Pichia pastoris along with caffeic acid biosynthesis genes resulted in a strain that is autoluminescent in standard media. We analyzed evolution of the enzymes of the luciferin biosynthesis cycle and found that fungal bioluminescence emerged through a series of events that included two independent gene duplications. The retention of the duplicated enzymes of the luciferin pathway in nonluminescent fungi shows that the gene duplication was followed by functional sequence divergence of enzymes of at least one gene in the biosynthetic pathway and suggests that the evolution of fungal bioluminescence proceeded through several closely related stepping stone nonluminescent biochemical reactions with adaptive roles. The availability of a complete eukaryotic luciferin biosynthesis pathway provides several applications in biomedicine and bioengineering."}],"has_accepted_license":"1","file":[{"file_id":"5926","date_updated":"2020-07-14T12:47:11Z","creator":"dernst","file_size":1271988,"date_created":"2019-02-05T15:21:40Z","checksum":"46b2c12185eb2ddb598f4c7b4bd267bf","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"2018_PNAS_Kotlobay.pdf"}],"department":[{"_id":"FyKo"}],"month":"12","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","issue":"50","citation":{"short":"A.A. Kotlobay, K. Sarkisyan, Y.A. Mokrushina, M. Marcet-Houben, E.O. Serebrovskaya, N.M. Markina, L. Gonzalez Somermeyer, A.Y. Gorokhovatsky, A. Vvedensky, K.V. Purtov, V.N. Petushkov, N.S. Rodionova, T.V. Chepurnyh, L. Fakhranurova, E.B. Guglya, R. Ziganshin, A.S. Tsarkova, Z.M. Kaskova, V. Shender, M. Abakumov, T.O. Abakumova, I.S. Povolotskaya, F.M. Eroshkin, A.G. Zaraisky, A.S. Mishin, S.V. Dolgov, T.Y. Mitiouchkina, E.P. Kopantzev, H.E. Waldenmaier, A.G. Oliveira, Y. Oba, E. Barsova, E.A. Bogdanova, T. Gabaldón, C.V. Stevani, S. Lukyanov, I.V. Smirnov, J.I. Gitelson, F. Kondrashov, I.V. Yampolsky, Proceedings of the National Academy of Sciences of the United States of America 115 (2018) 12728–12732.","ieee":"A. A. Kotlobay <i>et al.</i>, “Genetically encodable bioluminescent system from fungi,” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 115, no. 50. National Academy of Sciences, pp. 12728–12732, 2018.","ama":"Kotlobay AA, Sarkisyan K, Mokrushina YA, et al. Genetically encodable bioluminescent system from fungi. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 2018;115(50):12728-12732. doi:<a href=\"https://doi.org/10.1073/pnas.1803615115\">10.1073/pnas.1803615115</a>","mla":"Kotlobay, Alexey A., et al. “Genetically Encodable Bioluminescent System from Fungi.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 115, no. 50, National Academy of Sciences, 2018, pp. 12728–32, doi:<a href=\"https://doi.org/10.1073/pnas.1803615115\">10.1073/pnas.1803615115</a>.","apa":"Kotlobay, A. A., Sarkisyan, K., Mokrushina, Y. A., Marcet-Houben, M., Serebrovskaya, E. O., Markina, N. M., … Yampolsky, I. V. (2018). Genetically encodable bioluminescent system from fungi. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.1803615115\">https://doi.org/10.1073/pnas.1803615115</a>","ista":"Kotlobay AA, Sarkisyan K, Mokrushina YA, Marcet-Houben M, Serebrovskaya EO, Markina NM, Gonzalez Somermeyer L, Gorokhovatsky AY, Vvedensky A, Purtov KV, Petushkov VN, Rodionova NS, Chepurnyh TV, Fakhranurova L, Guglya EB, Ziganshin R, Tsarkova AS, Kaskova ZM, Shender V, Abakumov M, Abakumova TO, Povolotskaya IS, Eroshkin FM, Zaraisky AG, Mishin AS, Dolgov SV, Mitiouchkina TY, Kopantzev EP, Waldenmaier HE, Oliveira AG, Oba Y, Barsova E, Bogdanova EA, Gabaldón T, Stevani CV, Lukyanov S, Smirnov IV, Gitelson JI, Kondrashov F, Yampolsky IV. 2018. Genetically encodable bioluminescent system from fungi. Proceedings of the National Academy of Sciences of the United States of America. 115(50), 12728–12732.","chicago":"Kotlobay, Alexey A., Karen Sarkisyan, Yuliana A. Mokrushina, Marina Marcet-Houben, Ekaterina O. Serebrovskaya, Nadezhda M. Markina, Louisa Gonzalez Somermeyer, et al. “Genetically Encodable Bioluminescent System from Fungi.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences, 2018. <a href=\"https://doi.org/10.1073/pnas.1803615115\">https://doi.org/10.1073/pnas.1803615115</a>."},"language":[{"iso":"eng"}],"oa":1,"type":"journal_article","date_updated":"2023-09-11T14:04:05Z","_id":"5780","publisher":"National Academy of Sciences","doi":"10.1073/pnas.1803615115","article_processing_charge":"No","quality_controlled":"1","ddc":["580"],"page":"12728-12732","external_id":{"isi":["000452866000068"]},"year":"2018","isi":1,"date_published":"2018-12-11T00:00:00Z","status":"public","publication":"Proceedings of the National Academy of Sciences of the United States of America"}]