News

50 years of Metabolic Control Analysis: marking the anniversary

• 2023 was the 50th anniversary of the publication in 1973 of the papers by Kacser & Burns and Heinrich & Rapoport that led to the emergence of Metabolic Control Analysis as a distinct field. Following discussions between a section of the community, two initiatives were taken to mark this.

• BioSytems has published a Special Issue "50 years of Metabolic Control Analysis: its past and current influence in the biological sciences" comprising an editorial with dedication plus a mix of 15 reviews and original articles that have appeared in the journal during 2023. The Special Issue as an entity can be accessed directly at https://www.sciencedirect.com/journal/biosystems/special-issue/10MQP4T2TFL .

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• Interfaces Focus has published a themed issue on 50 years of Metabolic Control Analysis organised by Herbert Sauro. It includes a historical note by Tom Rapoport on the origins of the original research in Berlin.

Latest papers:

1. David Fell, David Taylor, Randall Weselake and John Harwood (2023) Metabolic Control Analysis of triacylglycerol accumulation in oilseed rape BioSystems, 10495 https://www.sciencedirect.com/science/article/pii/S0303264723000801

2. Emily Stoakes, George Savva, Ruby Coates, Noemi Tejera, Mark Poolman, Andrew J Grant, John Wain, Dipali Singh (2022) Substrate utilisation and energy metabolism in non-growing Campylobacter jejuni M1cam. Microorganisms, 10 (7), 1355, 2022. https://doi.org/10.3390/microorganisms10071355

3. Pearcy N, Garavaglia M, Millat T, Gilbert JP, Song Y, Hartman H, Woods C, Tomi-Andrino C, Bommareddy RR, Cho BK, Fell DA, Poolman M, King JR, Winzer K, Twycross J, Minton NP (2022) A genome-scale metabolic model of Cupriavidus necator H16 integrated with TraDIS and transcriptomic data reveals metabolic insights for biotechnological applications. PLoS Comput Biol 18(5): e1010106. https://doi.org/10.1371/journal.pcbi.1010106

4. Stepan Fenyk, Helen K. Woodfield, Trevor B. Romsdahl, Emma J. Wallington, Ruth E. Bates, David A. Fell, Kent D. Chapman, Tony Fawcett and John L. Harwood. Overexpression of phospholipid: diacylglycerol acyltransferase in Brassica napus results in changes in lipid metabolism and oil accumulation. Biochemical Journal 479 (6), 805-823 (2022): https://doi.org/10.1042/BCJ20220003

5. Díaz Calvo T, Tejera N, McNamara I, Langridge GC, Wain J, Poolman M, Singh D. Genome-Scale Metabolic Modelling Approach to Understand the Metabolism of the Opportunistic Human Pathogen Staphylococcus epidermidis RP62A. Metabolites. (2022); 12(2):136. https://doi.org/10.3390/metabo12020136

6. Valeria Villanova, Dipali Singh, Julien Pagliardini, David Fell, Adeline Le Monnier, Giovanni Finazzi and Mark Poolman. Boosting Biomass Quantity and Quality by Improved Mixotrophic Culture of the Diatom Phaeodactylum tricornutum. Frontiers in Plant Science, 12, 411 (2021). https://doi.org/10.3389/fpls.2021.642199

7. Noemi Tejera, Lisa Crossman, Bruce Pearson, Emily Stoakes, Fauzy Nasher, Bilal Djeghout, Mark Poolman, John Wain, Dipali Singh. Genome-scale metabolic model driven design of a defined medium for Campylobacter jejuni M1cam. Frontiers in Microbiology, 11, 1072 (2020). https://doi.org/10.3389/fmicb.2020.01072

8. Thea SB Møller, Gang Liu, Hassan B Hartman, Martin H Rau, Sisse Mortensen, Kristian Thamsborg, Andreas E Johansen, Morten OA Sommer, Luca Guardabassi, Mark G Poolman, John E Olsen. Global responses to oxytetracycline treatment in tetracycline-resistant Escherichia coli. Sci Rep 10, 8438 (2020). https://doi.org/10.1038/s41598-020-64995-1

9. Lieven, C., Beber, M.E., Olivier, B.G., Poolman M.G et al. MEMOTE for standardized genome-scale metabolic model testing. Nat Biotechnol 38, 272–276 (2020). https://doi.org/10.1038/s41587-020-0446-y

Previous papers:

• Woodfield, Helen; Fenyk, Stepan; Wallington, Emma; Bates, Ruth; Brown, Alexander; Guschina, Irina; Marillia, Elizabeth; Taylor, David; Fell, David; Harwood, John; Fawcett, Tony. Increase in lysophosphatidate acyltransferase activity in oilseed rape (Brassica napus L.) increases seed triacylglycerol content despite its low intrinsic flux control coefficient. New Phytologist, 224, 700-711 (2019). https://doi.org/10.1111/nph.16100

• Rupert O. J. Norman, Thomas Millat, Sarah Schatschneider, Anne M. Henstra, Ronja Breitkopf, Bart Pander, Florence J. Annan, Pawel Piatek, Hassan B. Hartman, Mark G. Poolman, David A.Fell, Klaus Winzer, Nigel P. Minton and Charlie Hodgman. A genome-scale model of Clostridium autoethanogenum reveals optimal bioprocess conditions for .high-value chemical production from carbon monoxide. Engineering Biology, 3:32 (2019). Open Access https://doi.org/10.1049/enb.2018.5003

• Pfau, Christian, Masakapalli, Poolman, Sweetlove & Ebenhoe. The intertwined metabolism during symbiotic nitrogen fixation elucidated by metabolic modelling. Nature Scientific Reports, 8:12504(2018) https://www.nature.com/articles/s41598-018-30884-x DOI

• Zia Fatma, Hassan Hartman, Mark G. Poolman, David A. Fell, Shireesh Srivastava , Tabinda Shakeela and Syed Shams ⁠Yazdani. Model-assisted metabolic engineering of Escherichia coli for long chain alkane and alcohol production, Metabolic Engineering, 45, 134-141 (2018). DOI

Background

• Our group began nearly forty years ago with initial interests in computer simulation of metabolism and the theoretical analysis of metabolic control and regulation. Whilst these still remain areas of interest, we have since developed interests in modelling signal transduction, in various different approaches to network analysis of metabolism, and in reconstructing metabolic networks from genomic data. In the course of this research, we have addressed problems in microbial, plant and mammalian metabolism, often in conjunction with collaborators who have contributed experimental results.

• Our current work centres on modelling the networks of reactions in cells, with particular emphasis on metabolism. It forms part of the emerging field of Systems Biology, in that we are concerned with understanding how biological function arises from the interactions between many components, and with building predictive models. We have to develop and apply suitable theoretical tools, including metabolic control analysis, computer simulation and other forms of algebraic and numerical analysis. In addition, we are investigating how to decipher the metabolic information contained in genome sequences. We are involved in projects on microbial, plant and animal metabolism, each in collaboration with an experimental team.
• Potential applications of our work include the design of changes in cellular metabolism to improve the output of product such as antibiotics, detecting vulnerable sites in cellular networks that could be targets for drugs to control disease-causing organisms, and improved understanding of how organisms manage to adjust their metabolism in response to environmental changes and other signals.

Related Sites

We also used to host the following web sites related to our research, but these are currently off-line.:

• The former website of the International Study Group for Systems Biology (at ://sysbio.brookes.ac.uk)
  In the interests of recording some of the history of the ISGSB and the BioThermoKinetics workshops, two pages from the former site are available here.

• The website for the Metabolic Pathways Analysis series of meetings (at ://mpa.brookes.ac.uk)