---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '15179'
abstract:
- lang: eng
  text: The fungal bioluminescence pathway can be reconstituted in other organisms
    allowing luminescence imaging without exogenously supplied substrate. The pathway
    starts from hispidin biosynthesis—a step catalyzed by a large fungal polyketide
    synthase that requires a posttranslational modification for activity. Here, we
    report identification of alternative compact hispidin synthases encoded by a phylogenetically
    diverse group of plants. A hybrid bioluminescence pathway that combines plant
    and fungal genes is more compact, not dependent on availability of machinery for
    posttranslational modifications, and confers autonomous bioluminescence in yeast,
    mammalian, and plant hosts. The compact size of plant hispidin synthases enables
    additional modes of delivery of autoluminescence, such as delivery with viral
    vectors.
acknowledgement: "We thank Milaboratory (milaboratory.com) for the access to computing
  and storage infrastructure. We thank J. Petrasek for providing the BY-2 cell culture
  line. We thank Konstantin Lukyanov laboratory and Sergey Deyev laboratory for assistance
  with experiments.\r\nThis study was partially funded by Light Bio and Planta. The
  Synthetic biology Group is funded by the MRC London Institute of Medical Sciences
  (UKRI MC-A658-5QEA0). Cloning and luminescent assays performed in BY-2 were partially
  supported by RSF, project number 22-14-00400, https://rscf.ru/project/22-14-00400/.
  Plant transformations were funded by RFBR and MOST, project number 21-54-52004.
  Plant imaging experiments were funded by RSF, project number 22-74-00124, https://rscf.ru/project/22-74-00124/.
  Viral delivery experiments were funded by the grant PID2019-108203RB-I00 Plan Nacional
  I + D from the Ministerio de Ciencia e Innovación (Spain) through the Agencia Estatal
  de Investigación (cofinanced by the European Regional Development Fund)."
article_number: adk1992
article_processing_charge: Yes
article_type: original
author:
- first_name: Kseniia A.
  full_name: Palkina, Kseniia A.
  last_name: Palkina
- first_name: Tatiana A.
  full_name: Karataeva, Tatiana A.
  last_name: Karataeva
- first_name: Maxim M.
  full_name: Perfilov, Maxim M.
  last_name: Perfilov
- first_name: Liliia I.
  full_name: Fakhranurova, Liliia I.
  last_name: Fakhranurova
- first_name: Nadezhda M.
  full_name: Markina, Nadezhda M.
  last_name: Markina
- first_name: Louisa
  full_name: Gonzalez Somermeyer, Louisa
  id: 4720D23C-F248-11E8-B48F-1D18A9856A87
  last_name: Gonzalez Somermeyer
  orcid: 0000-0001-9139-5383
- first_name: Elena
  full_name: Garcia-Perez, Elena
  last_name: Garcia-Perez
- first_name: Marta
  full_name: Vazquez-Vilar, Marta
  last_name: Vazquez-Vilar
- first_name: Marta
  full_name: Rodriguez-Rodriguez, Marta
  last_name: Rodriguez-Rodriguez
- first_name: Victor
  full_name: Vazquez-Vilriales, Victor
  last_name: Vazquez-Vilriales
- first_name: Ekaterina S.
  full_name: Shakhova, Ekaterina S.
  last_name: Shakhova
- first_name: Tatiana
  full_name: Mitiouchkina, Tatiana
  last_name: Mitiouchkina
- first_name: Olga A.
  full_name: Belozerova, Olga A.
  last_name: Belozerova
- first_name: Sergey I.
  full_name: Kovalchuk, Sergey I.
  last_name: Kovalchuk
- first_name: Anna
  full_name: Alekberova, Anna
  last_name: Alekberova
- first_name: Alena K.
  full_name: Malyshevskaia, Alena K.
  last_name: Malyshevskaia
- first_name: Evgenia N.
  full_name: Bugaeva, Evgenia N.
  last_name: Bugaeva
- first_name: Elena B.
  full_name: Guglya, Elena B.
  last_name: Guglya
- first_name: Anastasia
  full_name: Balakireva, Anastasia
  last_name: Balakireva
- first_name: Nikita
  full_name: Sytov, Nikita
  last_name: Sytov
- first_name: Anastasia
  full_name: Bezlikhotnova, Anastasia
  last_name: Bezlikhotnova
- first_name: Daria I.
  full_name: Boldyreva, Daria I.
  last_name: Boldyreva
- first_name: Vladislav V.
  full_name: Babenko, Vladislav V.
  last_name: Babenko
- first_name: Fyodor
  full_name: Kondrashov, Fyodor
  id: 44FDEF62-F248-11E8-B48F-1D18A9856A87
  last_name: Kondrashov
  orcid: 0000-0001-8243-4694
- first_name: Vladimir V.
  full_name: Choob, Vladimir V.
  last_name: Choob
- first_name: Diego
  full_name: Orzaez, Diego
  last_name: Orzaez
- first_name: Ilia V.
  full_name: Yampolsky, Ilia V.
  last_name: Yampolsky
- first_name: Alexander S.
  full_name: Mishin, Alexander S.
  last_name: Mishin
- first_name: Karen S.
  full_name: Sarkisyan, Karen S.
  last_name: Sarkisyan
citation:
  ama: Palkina KA, Karataeva TA, Perfilov MM, et al. A hybrid pathway for self-sustained
    luminescence. <i>Science Advances</i>. 2024;10(10). doi:<a href="https://doi.org/10.1126/sciadv.adk1992">10.1126/sciadv.adk1992</a>
  apa: Palkina, K. A., Karataeva, T. A., Perfilov, M. M., Fakhranurova, L. I., Markina,
    N. M., Gonzalez Somermeyer, L., … Sarkisyan, K. S. (2024). A hybrid pathway for
    self-sustained luminescence. <i>Science Advances</i>. American Association for
    the Advancement of Science. <a href="https://doi.org/10.1126/sciadv.adk1992">https://doi.org/10.1126/sciadv.adk1992</a>
  chicago: Palkina, Kseniia A., Tatiana A. Karataeva, Maxim M. Perfilov, Liliia I.
    Fakhranurova, Nadezhda M. Markina, Louisa Gonzalez Somermeyer, Elena Garcia-Perez,
    et al. “A Hybrid Pathway for Self-Sustained Luminescence.” <i>Science Advances</i>.
    American Association for the Advancement of Science, 2024. <a href="https://doi.org/10.1126/sciadv.adk1992">https://doi.org/10.1126/sciadv.adk1992</a>.
  ieee: K. A. Palkina <i>et al.</i>, “A hybrid pathway for self-sustained luminescence,”
    <i>Science Advances</i>, vol. 10, no. 10. American Association for the Advancement
    of Science, 2024.
  ista: Palkina KA, Karataeva TA, Perfilov MM, Fakhranurova LI, Markina NM, Gonzalez
    Somermeyer L, Garcia-Perez E, Vazquez-Vilar M, Rodriguez-Rodriguez M, Vazquez-Vilriales
    V, Shakhova ES, Mitiouchkina T, Belozerova OA, Kovalchuk SI, Alekberova A, Malyshevskaia
    AK, Bugaeva EN, Guglya EB, Balakireva A, Sytov N, Bezlikhotnova A, Boldyreva DI,
    Babenko VV, Kondrashov F, Choob VV, Orzaez D, Yampolsky IV, Mishin AS, Sarkisyan
    KS. 2024. A hybrid pathway for self-sustained luminescence. Science Advances.
    10(10), adk1992.
  mla: Palkina, Kseniia A., et al. “A Hybrid Pathway for Self-Sustained Luminescence.”
    <i>Science Advances</i>, vol. 10, no. 10, adk1992, American Association for the
    Advancement of Science, 2024, doi:<a href="https://doi.org/10.1126/sciadv.adk1992">10.1126/sciadv.adk1992</a>.
  short: K.A. Palkina, T.A. Karataeva, M.M. Perfilov, L.I. Fakhranurova, N.M. Markina,
    L. Gonzalez Somermeyer, E. Garcia-Perez, M. Vazquez-Vilar, M. Rodriguez-Rodriguez,
    V. Vazquez-Vilriales, E.S. Shakhova, T. Mitiouchkina, O.A. Belozerova, S.I. Kovalchuk,
    A. Alekberova, A.K. Malyshevskaia, E.N. Bugaeva, E.B. Guglya, A. Balakireva, N.
    Sytov, A. Bezlikhotnova, D.I. Boldyreva, V.V. Babenko, F. Kondrashov, V.V. Choob,
    D. Orzaez, I.V. Yampolsky, A.S. Mishin, K.S. Sarkisyan, Science Advances 10 (2024).
date_created: 2024-03-25T08:54:33Z
date_published: 2024-03-01T00:00:00Z
date_updated: 2025-09-04T13:16:05Z
day: '01'
ddc:
- '580'
department:
- _id: FyKo
doi: 10.1126/sciadv.adk1992
external_id:
  isi:
  - '001187580500013'
  pmid:
  - '38457503'
file:
- access_level: open_access
  checksum: a19c43b260ea0bbaf895a29712e3153c
  content_type: application/pdf
  creator: dernst
  date_created: 2024-03-25T09:42:10Z
  date_updated: 2024-03-25T09:42:10Z
  file_id: '15185'
  file_name: 2024_ScienceAdv_Palkina.pdf
  file_size: 1499302
  relation: main_file
  success: 1
file_date_updated: 2024-03-25T09:42:10Z
has_accepted_license: '1'
intvolume: '        10'
isi: 1
issue: '10'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
publication: Science Advances
publication_identifier:
  eissn:
  - 2375-2548
publication_status: published
publisher: American Association for the Advancement of Science
quality_controlled: '1'
scopus_import: '1'
status: public
title: A hybrid pathway for self-sustained luminescence
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 10
year: '2024'
...
---
OA_place: publisher
_id: '17850'
abstract:
- lang: eng
  text: "Understanding the relationship between a given phenotype and its underlying
    genotype or genotypes is one of the most pressing challenges of biology, as it
    lies at the heart of not only basic understanding of evolutionary theory, but
    also of practical applications in medicine and bioengineering. Understanding this
    relationship is complicated by the ubiquitous phenomenon of epistasis, wherein
    mutation effects are dependent on their genetic context. Fitness landscapes —
    representations of phenotype as a function of genotype — are being increasingly
    used as a tool to study the effects and interactions of thousands of mutations,
    but are experimentally limited to exploring a small fraction of a protein’s theoretical
    sequence space. Furthermore, not all regions of said sequence space are necessarily
    equally informative. Thus, gene selection for landscape surveys should be carefully
    considered in order to maximize the usable output of necessarily limited data.\r\n\r\nIn
    this work, we analyzed the fitness landscapes of orthologous green fluorescent
    proteins from four different species, by systematically measuring the phenotype,
    fluorescence, of tens of thousands of mutant genotypes from each protein. These
    landscapes were highly heterogeneous, with some genes being mutationally robust
    and displaying epistasis only rarely, and others being highly epistatic and mutationally
    fragile. We used this data to train machine learning models to predict fluorescence
    from genotype. Although the training data contained almost exclusively genotypes
    with less than 3% sequence divergence from the original wild-type sequences, we
    were able to create novel, functional genotypes with up to 20% sequence divergence.
    Counterintuitively however, genes with high mutational robustness and rare epistasis
    were more difficult to introduce large numbers of mutations into, not less. This
    represents the first study of large-scale fitness landscapes of a protein family,
    and provides insights into how to approach future landscape surveys and their
    applications in novel protein design."
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: ScienComp
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Louisa
  full_name: Gonzalez Somermeyer, Louisa
  id: 4720D23C-F248-11E8-B48F-1D18A9856A87
  last_name: Gonzalez Somermeyer
  orcid: 0000-0001-9139-5383
citation:
  ama: Gonzalez Somermeyer L. Fitness landscapes of orthologous green fluorescent
    proteins. 2024. doi:<a href="https://doi.org/10.15479/at:ista:17850">10.15479/at:ista:17850</a>
  apa: Gonzalez Somermeyer, L. (2024). <i>Fitness landscapes of orthologous green
    fluorescent proteins</i>. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/at:ista:17850">https://doi.org/10.15479/at:ista:17850</a>
  chicago: Gonzalez Somermeyer, Louisa. “Fitness Landscapes of Orthologous Green Fluorescent
    Proteins.” Institute of Science and Technology Austria, 2024. <a href="https://doi.org/10.15479/at:ista:17850">https://doi.org/10.15479/at:ista:17850</a>.
  ieee: L. Gonzalez Somermeyer, “Fitness landscapes of orthologous green fluorescent
    proteins,” Institute of Science and Technology Austria, 2024.
  ista: Gonzalez Somermeyer L. 2024. Fitness landscapes of orthologous green fluorescent
    proteins. Institute of Science and Technology Austria.
  mla: Gonzalez Somermeyer, Louisa. <i>Fitness Landscapes of Orthologous Green Fluorescent
    Proteins</i>. Institute of Science and Technology Austria, 2024, doi:<a href="https://doi.org/10.15479/at:ista:17850">10.15479/at:ista:17850</a>.
  short: L. Gonzalez Somermeyer, Fitness Landscapes of Orthologous Green Fluorescent
    Proteins, Institute of Science and Technology Austria, 2024.
corr_author: '1'
date_created: 2024-09-06T12:57:44Z
date_published: 2024-09-06T00:00:00Z
date_updated: 2026-04-07T13:25:01Z
day: '06'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: FyKo
doi: 10.15479/at:ista:17850
ec_funded: 1
file:
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file_date_updated: 2024-09-27T10:34:34Z
has_accepted_license: '1'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
page: '89'
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 26580278-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '771209'
  name: Characterizing the fitness landscape on population and global scales
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  link:
  - relation: software
    url: https://github.com/aequorea238/Orthologous_GFP_Fitness_Peaks
  record:
  - id: '11448'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Fyodor
  full_name: Kondrashov, Fyodor
  id: 44FDEF62-F248-11E8-B48F-1D18A9856A87
  last_name: Kondrashov
  orcid: 0000-0001-8243-4694
title: Fitness landscapes of orthologous green fluorescent proteins
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...
---
_id: '11448'
abstract:
- lang: eng
  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.
acknowledged_ssus:
- _id: LifeSc
- _id: Bio
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."
article_number: '75842'
article_processing_charge: No
article_type: original
author:
- first_name: Louisa
  full_name: Gonzalez Somermeyer, Louisa
  id: 4720D23C-F248-11E8-B48F-1D18A9856A87
  last_name: Gonzalez Somermeyer
  orcid: 0000-0001-9139-5383
- first_name: Aubin
  full_name: Fleiss, Aubin
  last_name: Fleiss
- first_name: Alexander S
  full_name: Mishin, Alexander S
  last_name: Mishin
- first_name: Nina G
  full_name: Bozhanova, Nina G
  last_name: Bozhanova
- first_name: Anna A
  full_name: Igolkina, Anna A
  last_name: Igolkina
- first_name: Jens
  full_name: Meiler, Jens
  last_name: Meiler
- first_name: Maria-Elisenda
  full_name: Alaball Pujol, Maria-Elisenda
  last_name: Alaball Pujol
- first_name: Ekaterina V
  full_name: Putintseva, Ekaterina V
  last_name: Putintseva
- first_name: Karen S
  full_name: Sarkisyan, Karen S
  last_name: Sarkisyan
- first_name: Fyodor
  full_name: Kondrashov, Fyodor
  id: 44FDEF62-F248-11E8-B48F-1D18A9856A87
  last_name: Kondrashov
  orcid: 0000-0001-8243-4694
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>
  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>
  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>.
  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.
  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>.
  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).
corr_author: '1'
date_created: 2022-06-18T09:06:59Z
date_published: 2022-05-05T00:00:00Z
date_updated: 2026-04-07T13:25:01Z
day: '05'
ddc:
- '570'
department:
- _id: GradSch
- _id: FyKo
doi: 10.7554/elife.75842
ec_funded: 1
external_id:
  isi:
  - '000799197200001'
  pmid:
  - '35510622'
file:
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  checksum: 7573c28f44028ab0cc81faef30039e44
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  creator: dernst
  date_created: 2022-06-20T07:44:19Z
  date_updated: 2022-06-20T07:44:19Z
  file_id: '11454'
  file_name: 2022_eLife_Somermeyer.pdf
  file_size: 5297213
  relation: main_file
  success: 1
file_date_updated: 2022-06-20T07:44:19Z
has_accepted_license: '1'
intvolume: '        11'
isi: 1
keyword:
- General Immunology and Microbiology
- General Biochemistry
- Genetics and Molecular Biology
- General Medicine
- General Neuroscience
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 26580278-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '771209'
  name: Characterizing the fitness landscape on population and global scales
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
publication: eLife
publication_identifier:
  issn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
related_material:
  link:
  - relation: software
    url: https://github.com/aequorea238/Orthologous_GFP_Fitness_Peaks
  record:
  - id: '17850'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Heterogeneity of the GFP fitness landscape and data-driven protein design
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 11
year: '2022'
...
---
_id: '7889'
abstract:
- lang: eng
  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.
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."
article_processing_charge: No
article_type: original
author:
- first_name: Tatiana
  full_name: Mitiouchkina, Tatiana
  last_name: Mitiouchkina
- first_name: Alexander S.
  full_name: Mishin, Alexander S.
  last_name: Mishin
- first_name: Louisa
  full_name: Gonzalez Somermeyer, Louisa
  id: 4720D23C-F248-11E8-B48F-1D18A9856A87
  last_name: Gonzalez Somermeyer
  orcid: 0000-0001-9139-5383
- first_name: Nadezhda M.
  full_name: Markina, Nadezhda M.
  last_name: Markina
- first_name: Tatiana V.
  full_name: Chepurnyh, Tatiana V.
  last_name: Chepurnyh
- first_name: Elena B.
  full_name: Guglya, Elena B.
  last_name: Guglya
- first_name: Tatiana A.
  full_name: Karataeva, Tatiana A.
  last_name: Karataeva
- first_name: Kseniia A.
  full_name: Palkina, Kseniia A.
  last_name: Palkina
- first_name: Ekaterina S.
  full_name: Shakhova, Ekaterina S.
  last_name: Shakhova
- first_name: Liliia I.
  full_name: Fakhranurova, Liliia I.
  last_name: Fakhranurova
- first_name: Sofia V.
  full_name: Chekova, Sofia V.
  last_name: Chekova
- first_name: Aleksandra S.
  full_name: Tsarkova, Aleksandra S.
  last_name: Tsarkova
- first_name: Yaroslav V.
  full_name: Golubev, Yaroslav V.
  last_name: Golubev
- first_name: Vadim V.
  full_name: Negrebetsky, Vadim V.
  last_name: Negrebetsky
- first_name: Sergey A.
  full_name: Dolgushin, Sergey A.
  last_name: Dolgushin
- first_name: Pavel V.
  full_name: Shalaev, Pavel V.
  last_name: Shalaev
- first_name: Dmitry
  full_name: Shlykov, Dmitry
  last_name: Shlykov
- first_name: Olesya A.
  full_name: Melnik, Olesya A.
  last_name: Melnik
- first_name: Victoria O.
  full_name: Shipunova, Victoria O.
  last_name: Shipunova
- first_name: Sergey M.
  full_name: Deyev, Sergey M.
  last_name: Deyev
- first_name: Andrey I.
  full_name: Bubyrev, Andrey I.
  last_name: Bubyrev
- first_name: Alexander S.
  full_name: Pushin, Alexander S.
  last_name: Pushin
- first_name: Vladimir V.
  full_name: Choob, Vladimir V.
  last_name: Choob
- first_name: Sergey V.
  full_name: Dolgov, Sergey V.
  last_name: Dolgov
- first_name: Fyodor
  full_name: Kondrashov, Fyodor
  id: 44FDEF62-F248-11E8-B48F-1D18A9856A87
  last_name: Kondrashov
  orcid: 0000-0001-8243-4694
- first_name: Ilia V.
  full_name: Yampolsky, Ilia V.
  last_name: Yampolsky
- first_name: Karen S.
  full_name: Sarkisyan, Karen S.
  last_name: Sarkisyan
citation:
  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>
  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>
  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>.
  ieee: T. Mitiouchkina <i>et al.</i>, “Plants with genetically encoded autoluminescence,”
    <i>Nature Biotechnology</i>, vol. 38. Springer Nature, pp. 944–946, 2020.
  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.
  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>.
  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.
date_created: 2020-05-25T15:02:00Z
date_published: 2020-04-27T00:00:00Z
date_updated: 2025-04-14T07:49:47Z
day: '27'
ddc:
- '570'
department:
- _id: FyKo
doi: 10.1038/s41587-020-0500-9
ec_funded: 1
external_id:
  isi:
  - '000529298800003'
  pmid:
  - '32341562'
file:
- access_level: open_access
  checksum: 1b30467500ec6277229a875b06e196d0
  content_type: application/pdf
  creator: dernst
  date_created: 2020-08-28T08:57:07Z
  date_updated: 2021-03-02T23:30:03Z
  embargo: 2021-03-01
  file_id: '8316'
  file_name: 2020_NatureBiotech_Mitiouchkina.pdf
  file_size: 1180086
  relation: main_file
file_date_updated: 2021-03-02T23:30:03Z
has_accepted_license: '1'
intvolume: '        38'
isi: 1
language:
- iso: eng
month: '04'
oa: 1
oa_version: Submitted Version
page: 944-946
pmid: 1
project:
- _id: 26580278-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '771209'
  name: Characterizing the fitness landscape on population and global scales
publication: Nature Biotechnology
publication_identifier:
  eissn:
  - 1546-1696
  issn:
  - 1087-0156
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - relation: erratum
    url: https://doi.org/10.1038/s41587-020-0578-0
scopus_import: '1'
status: public
title: Plants with genetically encoded autoluminescence
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 38
year: '2020'
...
---
_id: '5780'
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.
article_processing_charge: No
author:
- first_name: Alexey A.
  full_name: Kotlobay, Alexey A.
  last_name: Kotlobay
- first_name: Karen
  full_name: Sarkisyan, Karen
  id: 39A7BF80-F248-11E8-B48F-1D18A9856A87
  last_name: Sarkisyan
  orcid: 0000-0002-5375-6341
- first_name: Yuliana A.
  full_name: Mokrushina, Yuliana A.
  last_name: Mokrushina
- first_name: Marina
  full_name: Marcet-Houben, Marina
  last_name: Marcet-Houben
- first_name: Ekaterina O.
  full_name: Serebrovskaya, Ekaterina O.
  last_name: Serebrovskaya
- first_name: Nadezhda M.
  full_name: Markina, Nadezhda M.
  last_name: Markina
- first_name: Louisa
  full_name: Gonzalez Somermeyer, Louisa
  id: 4720D23C-F248-11E8-B48F-1D18A9856A87
  last_name: Gonzalez Somermeyer
  orcid: 0000-0001-9139-5383
- first_name: Andrey Y.
  full_name: Gorokhovatsky, Andrey Y.
  last_name: Gorokhovatsky
- first_name: Andrey
  full_name: Vvedensky, Andrey
  last_name: Vvedensky
- first_name: Konstantin V.
  full_name: Purtov, Konstantin V.
  last_name: Purtov
- first_name: Valentin N.
  full_name: Petushkov, Valentin N.
  last_name: Petushkov
- first_name: Natalja S.
  full_name: Rodionova, Natalja S.
  last_name: Rodionova
- first_name: Tatiana V.
  full_name: Chepurnyh, Tatiana V.
  last_name: Chepurnyh
- first_name: Liliia
  full_name: Fakhranurova, Liliia
  last_name: Fakhranurova
- first_name: Elena B.
  full_name: Guglya, Elena B.
  last_name: Guglya
- first_name: Rustam
  full_name: Ziganshin, Rustam
  last_name: Ziganshin
- first_name: Aleksandra S.
  full_name: Tsarkova, Aleksandra S.
  last_name: Tsarkova
- first_name: Zinaida M.
  full_name: Kaskova, Zinaida M.
  last_name: Kaskova
- first_name: Victoria
  full_name: Shender, Victoria
  last_name: Shender
- first_name: Maxim
  full_name: Abakumov, Maxim
  last_name: Abakumov
- first_name: Tatiana O.
  full_name: Abakumova, Tatiana O.
  last_name: Abakumova
- first_name: Inna S.
  full_name: Povolotskaya, Inna S.
  last_name: Povolotskaya
- first_name: Fedor M.
  full_name: Eroshkin, Fedor M.
  last_name: Eroshkin
- first_name: Andrey G.
  full_name: Zaraisky, Andrey G.
  last_name: Zaraisky
- first_name: Alexander S.
  full_name: Mishin, Alexander S.
  last_name: Mishin
- first_name: Sergey V.
  full_name: Dolgov, Sergey V.
  last_name: Dolgov
- first_name: Tatiana Y.
  full_name: Mitiouchkina, Tatiana Y.
  last_name: Mitiouchkina
- first_name: Eugene P.
  full_name: Kopantzev, Eugene P.
  last_name: Kopantzev
- first_name: Hans E.
  full_name: Waldenmaier, Hans E.
  last_name: Waldenmaier
- first_name: Anderson G.
  full_name: Oliveira, Anderson G.
  last_name: Oliveira
- first_name: Yuichi
  full_name: Oba, Yuichi
  last_name: Oba
- first_name: Ekaterina
  full_name: Barsova, Ekaterina
  last_name: Barsova
- first_name: Ekaterina A.
  full_name: Bogdanova, Ekaterina A.
  last_name: Bogdanova
- first_name: Toni
  full_name: Gabaldón, Toni
  last_name: Gabaldón
- first_name: Cassius V.
  full_name: Stevani, Cassius V.
  last_name: Stevani
- first_name: Sergey
  full_name: Lukyanov, Sergey
  last_name: Lukyanov
- first_name: Ivan V.
  full_name: Smirnov, Ivan V.
  last_name: Smirnov
- first_name: Josef I.
  full_name: Gitelson, Josef I.
  last_name: Gitelson
- first_name: Fyodor
  full_name: Kondrashov, Fyodor
  id: 44FDEF62-F248-11E8-B48F-1D18A9856A87
  last_name: Kondrashov
  orcid: 0000-0001-8243-4694
- first_name: Ilia V.
  full_name: Yampolsky, Ilia V.
  last_name: Yampolsky
citation:
  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>
  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>
  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>.
  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.
  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.
  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>.
  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.
date_created: 2018-12-23T22:59:18Z
date_published: 2018-12-11T00:00:00Z
date_updated: 2025-07-10T11:52:58Z
day: '11'
ddc:
- '580'
department:
- _id: FyKo
doi: 10.1073/pnas.1803615115
external_id:
  isi:
  - '000452866000068'
file:
- access_level: open_access
  checksum: 46b2c12185eb2ddb598f4c7b4bd267bf
  content_type: application/pdf
  creator: dernst
  date_created: 2019-02-05T15:21:40Z
  date_updated: 2020-07-14T12:47:11Z
  file_id: '5926'
  file_name: 2018_PNAS_Kotlobay.pdf
  file_size: 1271988
  relation: main_file
file_date_updated: 2020-07-14T12:47:11Z
has_accepted_license: '1'
intvolume: '       115'
isi: 1
issue: '50'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: 12728-12732
publication: Proceedings of the National Academy of Sciences of the United States
  of America
publication_identifier:
  issn:
  - 0027-8424
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
scopus_import: '1'
status: public
title: Genetically encodable bioluminescent system from fungi
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 115
year: '2018'
...