---
_id: '12261'
abstract:
- lang: eng
text: 'Dose–response relationships are a general concept for quantitatively describing
biological systems across multiple scales, from the molecular to the whole-cell
level. A clinically relevant example is the bacterial growth response to antibiotics,
which is routinely characterized by dose–response curves. The shape of the dose–response
curve varies drastically between antibiotics and plays a key role in treatment,
drug interactions, and resistance evolution. However, the mechanisms shaping the
dose–response curve remain largely unclear. Here, we show in Escherichia coli
that the distinctively shallow dose–response curve of the antibiotic trimethoprim
is caused by a negative growth-mediated feedback loop: Trimethoprim slows growth,
which in turn weakens the effect of this antibiotic. At the molecular level, this
feedback is caused by the upregulation of the drug target dihydrofolate reductase
(FolA/DHFR). We show that this upregulation is not a specific response to trimethoprim
but follows a universal trend line that depends primarily on the growth rate,
irrespective of its cause. Rewiring the feedback loop alters the dose–response
curve in a predictable manner, which we corroborate using a mathematical model
of cellular resource allocation and growth. Our results indicate that growth-mediated
feedback loops may shape drug responses more generally and could be exploited
to design evolutionary traps that enable selection against drug resistance.'
acknowledged_ssus:
- _id: M-Shop
acknowledgement: This work was in part supported by Human Frontier Science Program
GrantRGP0042/2013, Marie Curie Career Integration Grant303507, AustrianScience Fund
(FWF) Grant P27201-B22, and German Research Foundation(DFG) Collaborative Research
Center (SFB)1310to TB. SAA was supportedby the European Union’s Horizon2020Research
and Innovation Programunder the Marie Skłodowska-Curie Grant agreement No707352.
We wouldlike to thank the Bollenbach group for regular fruitful discussions. We
areparticularly thankful for the technical assistance of Booshini Fernando andfor
discussions of the theoretical aspects with Gerrit Ansmann. We areindebted to Bor
Kavˇciˇc for invaluable advice, help with setting up theluciferase-based growth
monitoring system, and for sharing plasmids. Weacknowledge the IST Austria Miba
Machine Shop for their support inbuilding a housing for the stacker of the plate
reader, which enabled thehigh-throughput luciferase-based experiments. We are grateful
to RosalindAllen, Bor Kavˇciˇc and Dor Russ for feedback on the manuscript. Open
Accessfunding enabled and organized by Projekt DEAL.
article_number: e10490
article_processing_charge: No
article_type: original
author:
- first_name: Andreas
full_name: Angermayr, Andreas
id: 4677C796-F248-11E8-B48F-1D18A9856A87
last_name: Angermayr
orcid: 0000-0001-8619-2223
- first_name: Tin Yau
full_name: Pang, Tin Yau
last_name: Pang
- first_name: Guillaume
full_name: Chevereau, Guillaume
last_name: Chevereau
- first_name: Karin
full_name: Mitosch, Karin
id: 39B66846-F248-11E8-B48F-1D18A9856A87
last_name: Mitosch
- first_name: Martin J
full_name: Lercher, Martin J
last_name: Lercher
- first_name: Mark Tobias
full_name: Bollenbach, Mark Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
citation:
ama: Angermayr A, Pang TY, Chevereau G, Mitosch K, Lercher MJ, Bollenbach MT. Growth‐mediated
negative feedback shapes quantitative antibiotic response. Molecular Systems
Biology. 2022;18(9). doi:10.15252/msb.202110490
apa: Angermayr, A., Pang, T. Y., Chevereau, G., Mitosch, K., Lercher, M. J., &
Bollenbach, M. T. (2022). Growth‐mediated negative feedback shapes quantitative
antibiotic response. Molecular Systems Biology. Embo Press. https://doi.org/10.15252/msb.202110490
chicago: Angermayr, Andreas, Tin Yau Pang, Guillaume Chevereau, Karin Mitosch, Martin
J Lercher, and Mark Tobias Bollenbach. “Growth‐mediated Negative Feedback Shapes
Quantitative Antibiotic Response.” Molecular Systems Biology. Embo Press,
2022. https://doi.org/10.15252/msb.202110490.
ieee: A. Angermayr, T. Y. Pang, G. Chevereau, K. Mitosch, M. J. Lercher, and M.
T. Bollenbach, “Growth‐mediated negative feedback shapes quantitative antibiotic
response,” Molecular Systems Biology, vol. 18, no. 9. Embo Press, 2022.
ista: Angermayr A, Pang TY, Chevereau G, Mitosch K, Lercher MJ, Bollenbach MT. 2022.
Growth‐mediated negative feedback shapes quantitative antibiotic response. Molecular
Systems Biology. 18(9), e10490.
mla: Angermayr, Andreas, et al. “Growth‐mediated Negative Feedback Shapes Quantitative
Antibiotic Response.” Molecular Systems Biology, vol. 18, no. 9, e10490,
Embo Press, 2022, doi:10.15252/msb.202110490.
short: A. Angermayr, T.Y. Pang, G. Chevereau, K. Mitosch, M.J. Lercher, M.T. Bollenbach,
Molecular Systems Biology 18 (2022).
date_created: 2023-01-16T09:58:34Z
date_published: 2022-09-01T00:00:00Z
date_updated: 2023-08-04T09:51:49Z
day: '01'
ddc:
- '570'
department:
- _id: ToBo
doi: 10.15252/msb.202110490
external_id:
isi:
- '000856482800001'
file:
- access_level: open_access
checksum: 8b1d8f5ea20c8408acf466435fb6ae01
content_type: application/pdf
creator: dernst
date_created: 2023-01-30T09:49:55Z
date_updated: 2023-01-30T09:49:55Z
file_id: '12446'
file_name: 2022_MolecularSystemsBio_Angermayr.pdf
file_size: 1098812
relation: main_file
success: 1
file_date_updated: 2023-01-30T09:49:55Z
has_accepted_license: '1'
intvolume: ' 18'
isi: 1
issue: '9'
keyword:
- Applied Mathematics
- Computational Theory and Mathematics
- General Agricultural and Biological Sciences
- General Immunology and Microbiology
- General Biochemistry
- Genetics and Molecular Biology
- Information Systems
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
publication: Molecular Systems Biology
publication_identifier:
eissn:
- 1744-4292
publication_status: published
publisher: Embo Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Growth‐mediated negative feedback shapes quantitative antibiotic response
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 18
year: '2022'
...
---
_id: '520'
abstract:
- lang: eng
text: Cyanobacteria are mostly engineered to be sustainable cell-factories by genetic
manipulations alone. Here, by modulating the concentration of allosteric effectors,
we focus on increasing product formation without further burdening the cells with
increased expression of enzymes. Resorting to a novel 96-well microplate cultivation
system for cyanobacteria, and using lactate-producing strains of Synechocystis
PCC6803 expressing different l-lactate dehydrogenases (LDH), we titrated the effect
of 2,5-anhydro-mannitol supplementation. The latter acts in cells as a nonmetabolizable
analogue of fructose 1,6-bisphosphate, a known allosteric regulator of one of
the tested LDHs. In this strain (SAA023), we achieved over 2-fold increase of
lactate productivity. Furthermore, we observed that as carbon is increasingly
deviated during growth toward product formation, there is an increased fixation
rate in the population of spontaneous mutants harboring an impaired production
pathway. This is a challenge in the development of green cell factories, which
may be countered by the incorporation in biotechnological processes of strategies
such as the one pioneered here.
article_type: letter_note
author:
- first_name: Wei
full_name: Du, Wei
last_name: Du
- first_name: Andreas
full_name: Angermayr, Andreas
id: 4677C796-F248-11E8-B48F-1D18A9856A87
last_name: Angermayr
orcid: 0000-0001-8619-2223
- first_name: Joeri
full_name: Jongbloets, Joeri
last_name: Jongbloets
- first_name: Douwe
full_name: Molenaar, Douwe
last_name: Molenaar
- first_name: Herwig
full_name: Bachmann, Herwig
last_name: Bachmann
- first_name: Klaas
full_name: Hellingwerf, Klaas
last_name: Hellingwerf
- first_name: Filipe
full_name: Branco Dos Santos, Filipe
last_name: Branco Dos Santos
citation:
ama: Du W, Angermayr A, Jongbloets J, et al. Nonhierarchical flux regulation exposes
the fitness burden associated with lactate production in Synechocystis sp. PCC6803.
ACS Synthetic Biology. 2017;6(3):395-401. doi:10.1021/acssynbio.6b00235
apa: Du, W., Angermayr, A., Jongbloets, J., Molenaar, D., Bachmann, H., Hellingwerf,
K., & Branco Dos Santos, F. (2017). Nonhierarchical flux regulation exposes
the fitness burden associated with lactate production in Synechocystis sp. PCC6803.
ACS Synthetic Biology. American Chemical Society. https://doi.org/10.1021/acssynbio.6b00235
chicago: Du, Wei, Andreas Angermayr, Joeri Jongbloets, Douwe Molenaar, Herwig Bachmann,
Klaas Hellingwerf, and Filipe Branco Dos Santos. “Nonhierarchical Flux Regulation
Exposes the Fitness Burden Associated with Lactate Production in Synechocystis
Sp. PCC6803.” ACS Synthetic Biology. American Chemical Society, 2017. https://doi.org/10.1021/acssynbio.6b00235.
ieee: W. Du et al., “Nonhierarchical flux regulation exposes the fitness
burden associated with lactate production in Synechocystis sp. PCC6803,” ACS
Synthetic Biology, vol. 6, no. 3. American Chemical Society, pp. 395–401,
2017.
ista: Du W, Angermayr A, Jongbloets J, Molenaar D, Bachmann H, Hellingwerf K, Branco
Dos Santos F. 2017. Nonhierarchical flux regulation exposes the fitness burden
associated with lactate production in Synechocystis sp. PCC6803. ACS Synthetic
Biology. 6(3), 395–401.
mla: Du, Wei, et al. “Nonhierarchical Flux Regulation Exposes the Fitness Burden
Associated with Lactate Production in Synechocystis Sp. PCC6803.” ACS Synthetic
Biology, vol. 6, no. 3, American Chemical Society, 2017, pp. 395–401, doi:10.1021/acssynbio.6b00235.
short: W. Du, A. Angermayr, J. Jongbloets, D. Molenaar, H. Bachmann, K. Hellingwerf,
F. Branco Dos Santos, ACS Synthetic Biology 6 (2017) 395–401.
date_created: 2018-12-11T11:46:56Z
date_published: 2017-03-17T00:00:00Z
date_updated: 2021-01-12T08:01:21Z
day: '17'
department:
- _id: ToBo
doi: 10.1021/acssynbio.6b00235
external_id:
pmid:
- '27936615'
intvolume: ' 6'
issue: '3'
language:
- iso: eng
month: '03'
oa_version: None
page: 395 - 401
pmid: 1
publication: ACS Synthetic Biology
publication_identifier:
issn:
- '21615063'
publication_status: published
publisher: American Chemical Society
publist_id: '7298'
quality_controlled: '1'
scopus_import: 1
status: public
title: Nonhierarchical flux regulation exposes the fitness burden associated with
lactate production in Synechocystis sp. PCC6803
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 6
year: '2017'
...
---
_id: '1061'
abstract:
- lang: eng
text: 'Background: Metabolic engineering and synthetic biology of cyanobacteria
offer a promising sustainable alternative approach for fossil-based ethylene production,
by using sunlight via oxygenic photosynthesis, to convert carbon dioxide directly
into ethylene. Towards this, both well-studied cyanobacteria, i.e., Synechocystis
sp PCC 6803 and Synechococcus elongatus PCC 7942, have been engineered to produce
ethylene by introducing the ethylene-forming enzyme (Efe) from Pseudomonas syringae
pv. phaseolicola PK2 (the Kudzu strain), which catalyzes the conversion of the
ubiquitous tricarboxylic acid cycle intermediate 2-oxoglutarate into ethylene.
Results: This study focuses on Synechocystis sp PCC 6803 and shows stable ethylene
production through the integration of a codon-optimized version of the efe gene
under control of the Ptrc promoter and the core Shine-Dalgarno sequence (5\''-AGGAGG-3\'')
as the ribosome-binding site (RBS), at the slr0168 neutral site. We have increased
ethylene production twofold by RBS screening and further investigated improving
ethylene production from a single gene copy of efe, using multiple tandem promoters
and by putting our best construct on an RSF1010-based broad-host-self-replicating
plasmid, which has a higher copy number than the genome. Moreover, to raise the
intracellular amounts of the key Efe substrate, 2-oxoglutarate, from which ethylene
is formed, we constructed a glycogen-synthesis knockout mutant (glgC) and introduced
the ethylene biosynthetic pathway in it. Under nitrogen limiting conditions, the
glycogen knockout strain has increased intracellular 2-oxoglutarate levels; however,
surprisingly, ethylene production was lower in this strain than in the wild-type
background. Conclusion: Making use of different RBS sequences, production of ethylene
ranging over a 20-fold difference has been achieved. However, a further increase
of production through multiple tandem promoters and a broad-host plasmid was not
achieved speculating that the transcription strength and the gene copy number
are not the limiting factors in our system.'
article_number: '34'
article_processing_charge: No
author:
- first_name: Vinod
full_name: Veetil, Vinod
last_name: Veetil
- first_name: Andreas
full_name: Angermayr, Andreas
id: 4677C796-F248-11E8-B48F-1D18A9856A87
last_name: Angermayr
orcid: 0000-0001-8619-2223
- first_name: Klaas
full_name: Hellingwerf, Klaas
last_name: Hellingwerf
citation:
ama: Veetil V, Angermayr A, Hellingwerf K. Ethylene production with engineered Synechocystis
sp PCC 6803 strains. Microbial Cell Factories. 2017;16(1). doi:10.1186/s12934-017-0645-5
apa: Veetil, V., Angermayr, A., & Hellingwerf, K. (2017). Ethylene production
with engineered Synechocystis sp PCC 6803 strains. Microbial Cell Factories.
BioMed Central. https://doi.org/10.1186/s12934-017-0645-5
chicago: Veetil, Vinod, Andreas Angermayr, and Klaas Hellingwerf. “Ethylene Production
with Engineered Synechocystis Sp PCC 6803 Strains.” Microbial Cell Factories.
BioMed Central, 2017. https://doi.org/10.1186/s12934-017-0645-5.
ieee: V. Veetil, A. Angermayr, and K. Hellingwerf, “Ethylene production with engineered
Synechocystis sp PCC 6803 strains,” Microbial Cell Factories, vol. 16,
no. 1. BioMed Central, 2017.
ista: Veetil V, Angermayr A, Hellingwerf K. 2017. Ethylene production with engineered
Synechocystis sp PCC 6803 strains. Microbial Cell Factories. 16(1), 34.
mla: Veetil, Vinod, et al. “Ethylene Production with Engineered Synechocystis Sp
PCC 6803 Strains.” Microbial Cell Factories, vol. 16, no. 1, 34, BioMed
Central, 2017, doi:10.1186/s12934-017-0645-5.
short: V. Veetil, A. Angermayr, K. Hellingwerf, Microbial Cell Factories 16 (2017).
date_created: 2018-12-11T11:49:56Z
date_published: 2017-02-23T00:00:00Z
date_updated: 2023-09-20T12:09:21Z
day: '23'
ddc:
- '579'
doi: 10.1186/s12934-017-0645-5
extern: '1'
external_id:
isi:
- '000397733000001'
pmid:
- '28231787'
file:
- access_level: open_access
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:16:50Z
date_updated: 2018-12-12T10:16:50Z
file_id: '5240'
file_name: IST-2017-792-v1+1_s12934-017-0645-5.pdf
file_size: 1361313
relation: main_file
file_date_updated: 2018-12-12T10:16:50Z
has_accepted_license: '1'
intvolume: ' 16'
isi: 1
issue: '1'
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
pmid: 1
publication: Microbial Cell Factories
publication_identifier:
issn:
- '14752859'
publication_status: published
publisher: BioMed Central
publist_id: '6325'
pubrep_id: '792'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Ethylene production with engineered Synechocystis sp PCC 6803 strains
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: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 16
year: '2017'
...
---
_id: '1218'
abstract:
- lang: eng
text: Investigating the physiology of cyanobacteria cultured under a diel light
regime is relevant for a better understanding of the resulting growth characteristics
and for specific biotechnological applications that are foreseen for these photosynthetic
organisms. Here, we present the results of a multiomics study of the model cyanobacterium
Synechocystis sp. strain PCC 6803, cultured in a lab-scale photobioreactor in
physiological conditions relevant for large-scale culturing. The culture was sparged
withN2 andCO2, leading to an anoxic environment during the dark period. Growth
followed the availability of light. Metabolite analysis performed with 1Hnuclear
magnetic resonance analysis showed that amino acids involved in nitrogen and sulfur
assimilation showed elevated levels in the light. Most protein levels, analyzed
through mass spectrometry, remained rather stable. However, several high-light-response
proteins and stress-response proteins showed distinct changes at the onset of
the light period. Microarray-based transcript analysis found common patterns of~56%
of the transcriptome following the diel regime. These oscillating transcripts
could be grouped coarsely into genes that were upregulated and downregulated in
the dark period. The accumulated glycogen was degraded in the anaerobic environment
in the dark. A small part was degraded gradually, reflecting basic maintenance
requirements of the cells in darkness. Surprisingly, the largest part was degraded
rapidly in a short time span at the end of the dark period. This degradation could
allow rapid formation of metabolic intermediates at the end of the dark period,
preparing the cells for the resumption of growth at the start of the light period.
acknowledgement: "Dutch Ministry of Economic Affairs, Agriculture, and Innovation
through the program BioSolar CellsS. Andreas Angermayr,Pascal van Alphen, Klaas
J. Hellingwerf\r\nWe thank Naira Quintana (presently at Rousselot, Belgium) for
the ini-\r\ntiative at the 10th Cyanobacterial Molecular Biology Workshop\r\n(CMBW),
June 2010, Lake Arrowhead, Los Angeles, CA, USA, to start the\r\ncollaborative endeavor
reported here. We thank Timo Maarleveld from\r\nCWI/VU (Amsterdam) for a custom-made
Python script handling the output from the NMR analysis and for evaluating and visualizing
the\r\nseparate metabolites for their evaluation. We thank Rob Verpoorte from\r\nLeiden
University (metabolome analysis) and Hans Aerts from the AMC\r\n(proteome analysis)
for lab space and equipment. We thank Robert Leh-\r\nmann (Humboldt University Berlin)
and Ilka Axmann (University of\r\nDüsseldorf) for sharing the R-code for the LOS
transformation of the\r\ntranscript data. We thank Hans C. P. Matthijs from IBED
for inspiring\r\ndialogues and insightful thoughts on continuous culturing of cyanobac-\r\nteria.
We thank Sandra Waaijenborg for performing the transcript nor-\r\nmalization and
Johan Westerhuis from BDA, Jeroen van der Steen and\r\nFilipe Branco dos Santos
from MMP, and Lucas Stal from IBED/NIOZ for\r\nhelpful discussions. We thank Milou
Schuurmans from MMP for help\r\nwith sampling and glycogen determination. We thank
the members of the\r\nRNA Biology & Applied Bioinformatics group at SILS, in particular
Selina\r\nvan Leeuwen, Elisa Hoekstra, and Martijs Jonker, for the microarray anal-\r\nysis.
We thank the reviewers of this work for their insightful comments\r\nwhich improved
the quality of the manuscript. This work, including the efforts of S. Andreas Angermayr,
Pascal van\r\nAlphen, and Klaas J. Hellingwerf, was funded by Dutch Ministry of
Eco-\r\nnomic Affairs, Agriculture, and Innovation through the program BioSolar\r\nCells."
author:
- first_name: Andreas
full_name: Angermayr, Andreas
id: 4677C796-F248-11E8-B48F-1D18A9856A87
last_name: Angermayr
orcid: 0000-0001-8619-2223
- first_name: Pascal
full_name: Van Alphen, Pascal
last_name: Van Alphen
- first_name: Dicle
full_name: Hasdemir, Dicle
last_name: Hasdemir
- first_name: Gertjan
full_name: Kramer, Gertjan
last_name: Kramer
- first_name: Muzamal
full_name: Iqbal, Muzamal
last_name: Iqbal
- first_name: Wilmar
full_name: Van Grondelle, Wilmar
last_name: Van Grondelle
- first_name: Huub
full_name: Hoefsloot, Huub
last_name: Hoefsloot
- first_name: Younghae
full_name: Choi, Younghae
last_name: Choi
- first_name: Klaas
full_name: Hellingwerf, Klaas
last_name: Hellingwerf
citation:
ama: Angermayr A, Van Alphen P, Hasdemir D, et al. Culturing synechocystis sp. Strain
pcc 6803 with N2 and CO2 in a diel regime reveals multiphase glycogen dynamics
with low maintenance costs. Applied and Environmental Microbiology. 2016;82(14):4180-4189.
doi:10.1128/AEM.00256-16
apa: Angermayr, A., Van Alphen, P., Hasdemir, D., Kramer, G., Iqbal, M., Van Grondelle,
W., … Hellingwerf, K. (2016). Culturing synechocystis sp. Strain pcc 6803 with
N2 and CO2 in a diel regime reveals multiphase glycogen dynamics with low maintenance
costs. Applied and Environmental Microbiology. American Society for Microbiology.
https://doi.org/10.1128/AEM.00256-16
chicago: Angermayr, Andreas, Pascal Van Alphen, Dicle Hasdemir, Gertjan Kramer,
Muzamal Iqbal, Wilmar Van Grondelle, Huub Hoefsloot, Younghae Choi, and Klaas
Hellingwerf. “Culturing Synechocystis Sp. Strain Pcc 6803 with N2 and CO2 in a
Diel Regime Reveals Multiphase Glycogen Dynamics with Low Maintenance Costs.”
Applied and Environmental Microbiology. American Society for Microbiology,
2016. https://doi.org/10.1128/AEM.00256-16.
ieee: A. Angermayr et al., “Culturing synechocystis sp. Strain pcc 6803 with
N2 and CO2 in a diel regime reveals multiphase glycogen dynamics with low maintenance
costs,” Applied and Environmental Microbiology, vol. 82, no. 14. American
Society for Microbiology, pp. 4180–4189, 2016.
ista: Angermayr A, Van Alphen P, Hasdemir D, Kramer G, Iqbal M, Van Grondelle W,
Hoefsloot H, Choi Y, Hellingwerf K. 2016. Culturing synechocystis sp. Strain pcc
6803 with N2 and CO2 in a diel regime reveals multiphase glycogen dynamics with
low maintenance costs. Applied and Environmental Microbiology. 82(14), 4180–4189.
mla: Angermayr, Andreas, et al. “Culturing Synechocystis Sp. Strain Pcc 6803 with
N2 and CO2 in a Diel Regime Reveals Multiphase Glycogen Dynamics with Low Maintenance
Costs.” Applied and Environmental Microbiology, vol. 82, no. 14, American
Society for Microbiology, 2016, pp. 4180–89, doi:10.1128/AEM.00256-16.
short: A. Angermayr, P. Van Alphen, D. Hasdemir, G. Kramer, M. Iqbal, W. Van Grondelle,
H. Hoefsloot, Y. Choi, K. Hellingwerf, Applied and Environmental Microbiology
82 (2016) 4180–4189.
date_created: 2018-12-11T11:50:46Z
date_published: 2016-07-01T00:00:00Z
date_updated: 2021-01-12T06:49:10Z
day: '01'
department:
- _id: ToBo
doi: 10.1128/AEM.00256-16
intvolume: ' 82'
issue: '14'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4959195/
month: '07'
oa: 1
oa_version: Submitted Version
page: 4180 - 4189
publication: Applied and Environmental Microbiology
publication_status: published
publisher: American Society for Microbiology
publist_id: '6117'
quality_controlled: '1'
scopus_import: 1
status: public
title: Culturing synechocystis sp. Strain pcc 6803 with N2 and CO2 in a diel regime
reveals multiphase glycogen dynamics with low maintenance costs
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 82
year: '2016'
...
---
_id: '1623'
abstract:
- lang: eng
text: "Background\r\nPhotosynthetic cyanobacteria are attractive for a range of
biotechnological applications including biofuel production. However, due to slow
growth, screening of mutant libraries using microtiter plates is not feasible.\r\nResults\r\nWe
present a method for high-throughput, single-cell analysis and sorting of genetically
engineered l-lactate-producing strains of Synechocystis sp. PCC6803. A microfluidic
device is used to encapsulate single cells in picoliter droplets, assay the droplets
for l-lactate production, and sort strains with high productivity. We demonstrate
the separation of low- and high-producing reference strains, as well as enrichment
of a more productive l-lactate-synthesizing population after UV-induced mutagenesis.
The droplet platform also revealed population heterogeneity in photosynthetic
growth and lactate production, as well as the presence of metabolically stalled
cells.\r\nConclusions\r\nThe workflow will facilitate metabolic engineering and
directed evolution studies and will be useful in studies of cyanobacteria biochemistry
and physiology.\r\n"
article_number: '193'
author:
- first_name: Petter
full_name: Hammar, Petter
last_name: Hammar
- first_name: Andreas
full_name: Angermayr, Andreas
id: 4677C796-F248-11E8-B48F-1D18A9856A87
last_name: Angermayr
orcid: 0000-0001-8619-2223
- first_name: Staffan
full_name: Sjostrom, Staffan
last_name: Sjostrom
- first_name: Josefin
full_name: Van Der Meer, Josefin
last_name: Van Der Meer
- first_name: Klaas
full_name: Hellingwerf, Klaas
last_name: Hellingwerf
- first_name: Elton
full_name: Hudson, Elton
last_name: Hudson
- first_name: Hakaan
full_name: Joensson, Hakaan
last_name: Joensson
citation:
ama: Hammar P, Angermayr A, Sjostrom S, et al. Single-cell screening of photosynthetic
growth and lactate production by cyanobacteria. Biotechnology for Biofuels.
2015;8(1). doi:10.1186/s13068-015-0380-2
apa: Hammar, P., Angermayr, A., Sjostrom, S., Van Der Meer, J., Hellingwerf, K.,
Hudson, E., & Joensson, H. (2015). Single-cell screening of photosynthetic
growth and lactate production by cyanobacteria. Biotechnology for Biofuels.
BioMed Central. https://doi.org/10.1186/s13068-015-0380-2
chicago: Hammar, Petter, Andreas Angermayr, Staffan Sjostrom, Josefin Van Der Meer,
Klaas Hellingwerf, Elton Hudson, and Hakaan Joensson. “Single-Cell Screening of
Photosynthetic Growth and Lactate Production by Cyanobacteria.” Biotechnology
for Biofuels. BioMed Central, 2015. https://doi.org/10.1186/s13068-015-0380-2.
ieee: P. Hammar et al., “Single-cell screening of photosynthetic growth and
lactate production by cyanobacteria,” Biotechnology for Biofuels, vol.
8, no. 1. BioMed Central, 2015.
ista: Hammar P, Angermayr A, Sjostrom S, Van Der Meer J, Hellingwerf K, Hudson E,
Joensson H. 2015. Single-cell screening of photosynthetic growth and lactate production
by cyanobacteria. Biotechnology for Biofuels. 8(1), 193.
mla: Hammar, Petter, et al. “Single-Cell Screening of Photosynthetic Growth and
Lactate Production by Cyanobacteria.” Biotechnology for Biofuels, vol.
8, no. 1, 193, BioMed Central, 2015, doi:10.1186/s13068-015-0380-2.
short: P. Hammar, A. Angermayr, S. Sjostrom, J. Van Der Meer, K. Hellingwerf, E.
Hudson, H. Joensson, Biotechnology for Biofuels 8 (2015).
date_created: 2018-12-11T11:53:05Z
date_published: 2015-11-25T00:00:00Z
date_updated: 2021-01-12T06:52:04Z
day: '25'
ddc:
- '570'
department:
- _id: ToBo
doi: 10.1186/s13068-015-0380-2
file:
- access_level: open_access
checksum: 172b0b6f4eb2e5c22b7cec1d57dc0107
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:10:11Z
date_updated: 2020-07-14T12:45:07Z
file_id: '4796'
file_name: IST-2016-467-v1+1_s13068-015-0380-2.pdf
file_size: 2914089
relation: main_file
file_date_updated: 2020-07-14T12:45:07Z
has_accepted_license: '1'
intvolume: ' 8'
issue: '1'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
publication: Biotechnology for Biofuels
publication_status: published
publisher: BioMed Central
publist_id: '5537'
pubrep_id: '467'
quality_controlled: '1'
scopus_import: 1
status: public
title: Single-cell screening of photosynthetic growth and lactate production by cyanobacteria
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: 8
year: '2015'
...
---
_id: '1586'
abstract:
- lang: eng
text: Through metabolic engineering cyanobacteria can be employed in biotechnology.
Combining the capacity for oxygenic photosynthesis and carbon fixation with an
engineered metabolic pathway allows carbon-based product formation from CO2, light,
and water directly. Such cyanobacterial 'cell factories' are constructed to produce
biofuels, bioplastics, and commodity chemicals. Efforts of metabolic engineers
and synthetic biologists allow the modification of the intermediary metabolism
at various branching points, expanding the product range. The new biosynthesis
routes 'tap' the metabolism ever more efficiently, particularly through the engineering
of driving forces and utilization of cofactors generated during the light reactions
of photosynthesis, resulting in higher product titers. High rates of carbon rechanneling
ultimately allow an almost-complete allocation of fixed carbon to product above
biomass.
author:
- first_name: Andreas
full_name: Angermayr, Andreas
id: 4677C796-F248-11E8-B48F-1D18A9856A87
last_name: Angermayr
orcid: 0000-0001-8619-2223
- first_name: Aleix
full_name: Gorchs, Aleix
last_name: Gorchs
- first_name: Klaas
full_name: Hellingwerf, Klaas
last_name: Hellingwerf
citation:
ama: Angermayr A, Gorchs A, Hellingwerf K. Metabolic engineering of cyanobacteria
for the synthesis of commodity products. Trends in Biotechnology. 2015;33(6):352-361.
doi:10.1016/j.tibtech.2015.03.009
apa: Angermayr, A., Gorchs, A., & Hellingwerf, K. (2015). Metabolic engineering
of cyanobacteria for the synthesis of commodity products. Trends in Biotechnology.
Elsevier. https://doi.org/10.1016/j.tibtech.2015.03.009
chicago: Angermayr, Andreas, Aleix Gorchs, and Klaas Hellingwerf. “Metabolic Engineering
of Cyanobacteria for the Synthesis of Commodity Products.” Trends in Biotechnology.
Elsevier, 2015. https://doi.org/10.1016/j.tibtech.2015.03.009.
ieee: A. Angermayr, A. Gorchs, and K. Hellingwerf, “Metabolic engineering of cyanobacteria
for the synthesis of commodity products,” Trends in Biotechnology, vol.
33, no. 6. Elsevier, pp. 352–361, 2015.
ista: Angermayr A, Gorchs A, Hellingwerf K. 2015. Metabolic engineering of cyanobacteria
for the synthesis of commodity products. Trends in Biotechnology. 33(6), 352–361.
mla: Angermayr, Andreas, et al. “Metabolic Engineering of Cyanobacteria for the
Synthesis of Commodity Products.” Trends in Biotechnology, vol. 33, no.
6, Elsevier, 2015, pp. 352–61, doi:10.1016/j.tibtech.2015.03.009.
short: A. Angermayr, A. Gorchs, K. Hellingwerf, Trends in Biotechnology 33 (2015)
352–361.
date_created: 2018-12-11T11:52:52Z
date_published: 2015-06-01T00:00:00Z
date_updated: 2021-01-12T06:51:46Z
day: '01'
department:
- _id: ToBo
doi: 10.1016/j.tibtech.2015.03.009
intvolume: ' 33'
issue: '6'
language:
- iso: eng
month: '06'
oa_version: None
page: 352 - 361
publication: Trends in Biotechnology
publication_status: published
publisher: Elsevier
publist_id: '5585'
quality_controlled: '1'
scopus_import: 1
status: public
title: Metabolic engineering of cyanobacteria for the synthesis of commodity products
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 33
year: '2015'
...