The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Metabolic Flux Analysis in Synechocystis Using Isotope Distribution from 13C-Labeled Glucose
Abstract
Using the carbon isotope labeling technique, the response of cyanobacterial central carbon metabolism to the change in environmental conditions was investigated. Synechocystis was grown in the heterotrophic and mixotrophic cultures fed with 13C-labeled glucose. The labeling patterns of the amino acids in biomass hydrolysates for both cultures were detected by the two-dimensional 1H-13C correlation nuclear magnetic resonance (2D 1H-13C COSY NMR) spectroscopy and gas chromatography-mass spectrometry (GC-MS) technique. The in vivo intracellular flux distributions were then quantitated from the labeling measurements and metabolite balances using a parameters fitting approach. From the estimated flux distributions, it was found that the pentose phosphate pathway was the major pathway of glucose catabolism in the heterotrophic culture, while in the mixotrophic culture, the flux of CO2 fixation through the Calvin cycle was about two-fold of the glucose input flux. The relative flux through the phosphoenolpyruvate carboxylase was very high in both cultures, and this reaction represented about 25% of the assimilated CO2 in the mixotrophic culture. More importantly, we found a substantial outflow from the tricarboxylic acid cycle to glycolysis pathway carried by the malic enzyme, demonstrating the operation of a C4 pathway in cyanobacterial cells through the PEP carboxylase and malic enzyme. The estimated flux distributions also revealed that the NADPH synthesis was in excess relative to its requirement, and the excess NADPH might be reoxidized in cyanobacterial respiration to provide the energy for cellular requirement. Moreover, the analyzed result also suggested that the activity of the respiratory electron transport chain in cyanobacterial cells was not inhibited by light.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Although Rubisco is the main enzyme responsible for the C fixation, cyanobacteria possess an additional assimilation mechanism operated by phosphoenolpyruvate carboxylase (PEPC) and malic acid to assist them in the fixation of large amounts of CO2 which is similar to the C4 pathway in plants (Yang et al. 2002).”
From Renewable energy from Cyanobacteria: energy production optimization by metabolic pathway engineering (2011) · cites this paper as Yang et al. 2002
Citations
Cites
The Molecular Biology of Cyanobacteria
(1994) · Springer eBooks · doi:10.1007/978-94-011-0227-8 · Cited by 1,429
Ethanol Synthesis by Genetic Engineering in Cyanobacteria
Deng, M.-D., & Coleman, J. R. (1999) · Applied and Environmental Microbiology · doi:10.1128/aem.65.2.523-528.1999 · Cited by 457
Yang, C., Hua, Q., & Shimizu, K. (2000) · Biochemical Engineering Journal · doi:10.1016/s1369-703x(00)00080-2 · Cited by 428
Self-citationSauer, U., Lasko, D. R., Fiaux, J., Hochuli, M., Glaser, R. W., Szyperski, T., Kurt Wüthrich, A., & Bailey, J. E. (1999) · Journal of Bacteriology · doi:10.1128/jb.181.21.6679-6688.1999 · Cited by 371
Szyperski, T. (1995) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1995.tb20829.x · Cited by 367
Origin and ,evolution of organelle genomes
Gray, M. W. (1993) · Current Opinion in Genetics & Development · doi:10.1016/0959-437x(93)90009-e · Cited by 246
Modes of cyanobacterial carbon metabolism
Smith, A. J. (1983) · Research in Microbiology · doi:10.1016/s0769-2609(83)80099-4 · Cited by 242
Metabolic fluxes in riboflavin-producing Bacillus subtilis
Sauer, U., Vassily Hatzimanikatis, A., Bailey, J. E., Hochuli, M., Szyperski, T., & Kurt Wüthrich, A. (1997) · Nature Biotechnology · doi:10.1038/nbt0597-448 · Cited by 235
GC‐MS Analysis of Amino Acids Rapidly Provides Rich Information for Isotopomer Balancing
Dauner, M., & Sauer, U. (2000) · Biotechnology Progress · doi:10.1021/bp000058h · Cited by 234
Isotopomer Analysis Using GC-MS
Christensen, B. B., & NIELSEN, J. K. (1999) · Metabolic Engineering · doi:10.1006/mben.1999.0117 · Cited by 227
Cited by
Sorted by citations
Items 201–241 of 241
Tanaka, K., Kondo, A., & Hasunuma, T. (2024) · Plant and Cell Physiology · doi:10.1093/pcp/pcae102 · Cited by 2
Recent Advancement in Metabolomic Research: Applications and Limitations
Rawat, P., Singh, M., Punetha, S., & Pradhan, S. (2024) · Springer eBooks · doi:10.1007/978-981-97-4292-9_12 · Cited by 2
13C-Metabolic Flux Analysis and Metabolic Regulation
Matsuoka, Y., & Shimizu, K. (2012) · InTech eBooks · doi:10.5772/35121 · Cited by 2
Self-citationPositional 13C enrichment analysis of aspartate determines PEPC activity in vivo
Wittemeier, L., Rajarathinam, Y., Erban, A., Hagemann, M., & Kopka, J. (2025) · New Phytologist · doi:10.1111/nph.70412 · Cited by 1
Faulkner, M., Andrews, F., & Scrutton, N. S. (2025) · Biotechnology for Biofuels and Bioproducts · doi:10.1186/s13068-025-02718-2 · Cited by 1
Desarrollo de una plataforma computacional para el modelado metabólico de microorganismos
Chirino, R. R., González, J. G., Infante, R. A. J., Vázquez, V. C., Dopico, J. T., García, L. V., Castro-Palacio, J. C., de Córdoba, P. F., Schölzel, J. F. U., Navarro-Peris, E., et al. (2011) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) · Cited by 1
Osanai, T., Iijima, H., & Hirai, M. Y. (2016) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-3-319-25979-6_20 · Cited by 1
13 C-metabolic flux analysis and its applications
Shimizu, K. (2013) · Elsevier eBooks · doi:10.1533/9781908818201.263 · Cited by 1
Self-citationEngineering of redox metabolism in yeast: New strategies for improved glycerol production
Geertman, J.-M. A. (2006) · Data Archiving and Networked Services (DANS) · Cited by 1
What We Can Learn from Measuring Metabolic Fluxes in Cyanobacteria
Gao, X., Wu, C., Cantrell, M., Cano, M., Yu, J., & Xiong, W. (2021) · doi:10.1002/9783527824908.ch4 · Cited by 1
Fructose-1,6-bisphosphatase (FBPase) fine-tunes heterotrophic growth in cyanobacteriaPreprint
Caliebe, F., Ojha, R. S., Gruber, M., Boehm, M., Shen, L., Bräsen, C., Snoep, J. L., Forchhammer, K., Hagemann, M., Siebers, B., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.02.14.638281 · Cited by 1
In vivo RUBISCO activity in Synechocystis is regulated by RuBP availabilityPreprint
Wittemeier, L., Arrivault, S., Neumann, N., Maček, B., Schmidt, N., Hagemann, M., & Kopka, J. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.06.06.658252 · Cited by 1
Funktionelle Analyse der Phytochrome Cph1 und Cph2 von Synechocystis Sp. PCC 6803
Fiedler, B. (2005) · edoc Publication server (Humboldt University of Berlin) · doi:10.18452/15285
Biosynthesis of glucose‐ d ‐13C6 from Hansenula polymorpha and methanol‐13C
Liu, Z., Ren, Z., Xu, D., & Li, L. (2011) · Journal of Labelled Compounds and Radiopharmaceuticals · doi:10.1002/jlcr.1935
Liu, Z., Zhou, L., & Hua, Q. (2012) · PubMed
Self-citationFlux balance analysis to model microbial metabolism for electricity generation
Mao, L. (2013) · Lincoln University Research Archive (Lincoln University)
Transcriptional profiling and flux measurements of polyhydroxybutyrate production in Synechocystis
Silva, S. S. (2004) · DSpace@MIT (Massachusetts Institute of Technology)
oleaginous microalga Chlorella protothecoides
Xiong, W., Liu, L., Wu, C., Yang, C., & Wu, Q. (2010)
Self-citationSchwarzkopf, M., Yoo, Y. C., Hückelhoven, R., Park, Y. M., Proels, R. K., & Phytopathologie, L. F. (2014)
Towards stable cyanobacterial cell factories
Du, W. (2018) · UvA-DARE (University of Amsterdam)
Sensitive NMR method for detecting carbohydrate influx into competing chemocatalytic pathways
Elliot, S. G., Jessen, B. M., Taarning, E., Madsen, R., & Meier, S. (2020) · The Analyst · doi:10.1039/d0an00555j
Metabolic Network Analysis of Filamentous Cyanobacteria
Noreña-Caro, D. (2020) · Louisiana State University · doi:10.31390/gradschool_dissertations.5293
Chen, A. Y., Ku, J. T., Tsai, T. P., Hung, J. J.-C., Hung, B. C., & Lan, E. I. (2023) · Advances in biochemical engineering, biotechnology · doi:10.1007/10_2023_218
Kokila, V., Chakrabarti, B., & Prasanna, R. (2023) · Springer eBooks · doi:10.1007/978-981-99-2973-3_12
Tanaka, K., Kondo, A., & Hasunuma, T. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.10.18.562951
Electrochemical glucose biosensors based on microbial whole cells
Aslan, S., Oktay, M. K., & Özen, A. A. (2024) · Royal Society of Chemistry eBooks · doi:10.1039/9781837676408-00027
Decoding Metabolic Changes in Cancer Cells Resistant to Therapy
Noor, S., Ali, S., Summer, M., & Khan, K. (2025) · Interdisciplinary cancer research · doi:10.1007/16833_2025_496
Apolinário, G., Gonçalves, J., Cunha, E., Madureira, L., Maciel, F., Geada, P., & Dias, Ó. (2025) · Lecture notes in networks and systems · doi:10.1007/978-3-031-87873-2_18
Roles of mixotrophy and symbiosis and molecular mechanisms
Lin, S. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-15743-1.00006-6
Barone, G. D., Hubáček, M., Malihan‐Yap, L., Grimm, H. C., Nikkanen, L., Pacheco, C. C., Tamagnini, P., Allahverdiyeva, Y., & Kourist, R. (2024) · Figshare · doi:10.6084/m9.figshare.26559791
Schulze, D., Kohlstedt, M., Becker, J., Cahoreau, E., Peyriga, L., Makowka, A., Hildebrandt, S., Gutekunst, K., Portais, J., & Wittmann, C. (2022) · Figshare · doi:10.6084/m9.figshare.20375971
Xie, H., Kjellström, J., & Lindblad, P. C. (2023) · Figshare · doi:10.6084/m9.figshare.24113101
Meagher, M., Camacho, D. J., Gallaher, S. D., Merchant, S., & Boyle, N. R. (2026) · Metabolic Engineering · doi:10.1016/j.ymben.2026.01.007
Genome-Scale Metabolic Modeling of Terpenoid Biosynthesis: Advances and Perspectives
Cheng, M., Gao, X., Shen, R., Liang, X., Dai, Y., Guo, Q., & Ye, C. (2026) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.6c03926
Kokila, V., Prasanna, R., Kumar, A., Katral, A., Chawla, G., Nivedha, R. M., Nishanth, S., Muthusamy, V., Singh, B., & Singh, A. K. (2026) · Journal of Applied Phycology · doi:10.1007/s10811-026-03981-y
Metadata
- Authors
- Yang, C., Hua, Q., & Shimizu, K.
- Affiliations
- Institute for Advanced Biosciences, Keio University (JP)
- Kyushu Institute of Technology (JP)
- Corresponding author
- Shimizu, Kazuyuki
- Venue
- Metabolic Engineering
- Publisher
- Elsevier BV
- Published
- 2002-07
- Volume
- 4
- Issue
- 3
- Pages
- 202-216
- ISSN
- 1096-7176 (ISSN-L)
- OpenAlex
- W1490314836
- Cited by
- 241
- References
- 41
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 13 · 2023: 14 · 2022: 11 · 2021: 6 · 2020: 12 · 2019: 8 · 2018: 18 · 2017: 17 · 2016: 15 · 2015: 11 · 2014: 11 · 2013: 18 · 2012: 12
- FWCI
- 1.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Metabolic Engineering (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Photosynthetic Processes and Mechanisms
- Physical Sciences › Energy › Renewable Energy, Sustainability and the Environment › Algal biology and biofuel production
- Keywords
- Synechocystis, metabolic flux distribution, 13C-labeled glucose, pentose phosphate pathway, Calvin cycle, phosphoenolpyruvate carboxylase, malic enzyme, C4 photosynthesis, TCA cycle, NADPH production, heterotrophic culture, mixotrophic cultivation, CO2 fixation, respiratory electron transport chain
- MeSH terms
- Cyanobacteria, Amino Acids, Carbon, Carbon Radioisotopes, Cells, Cultured, Computer Simulation, Culture Media, Glucose, Hydrolysis, Isotope Labeling, Gas Chromatography-Mass Spectrometry, Models, Biological, Models, Chemical, Multienzyme Complexes, Species Specificity, Stereoisomerism, Nuclear Magnetic Resonance, Biomolecular
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review