guy poncing

Synthetic Biology underpins advances in the bioeconomy

Biological systems - including the simplest cells - exhibit a broad range of functions to thrive in their environment. Research in the Imperial College Centre for Synthetic Biology is focused on the possibility of engineering the underlying biochemical processes to solve many of the challenges facing society, from healthcare to sustainable energy. In particular, we model, analyse, design and build biological and biochemical systems in living cells and/or in cell extracts, both exploring and enhancing the engineering potential of biology. 

As part of our research we develop novel methods to accelerate the celebrated Design-Build-Test-Learn synthetic biology cycle. As such research in the Centre for Synthetic Biology highly multi- and interdisciplinary covering computational modelling and machine learning approaches; automated platform development and genetic circuit engineering ; multi-cellular and multi-organismal interactions, including gene drive and genome engineering; metabolic engineering; in vitro/cell-free synthetic biology; engineered phages and directed evolution; and biomimetics, biomaterials and biological engineering.

Publications

Citation

BibTex format

@article{Deshpande:2020:10.1007/s00422-020-00846-6,
author = {Deshpande, A and Ouldridge, T},
doi = {10.1007/s00422-020-00846-6},
journal = {Biological Cybernetics: communication and control in organisms and automata},
pages = {653--668},
title = {Optimizing enzymatic catalysts for rapid turnover of substrates with low enzyme sequestration},
url = {http://dx.doi.org/10.1007/s00422-020-00846-6},
volume = {114},
year = {2020}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Enzymes are central to both metabolism and information processing in cells. In both cases, an enzyme’s ability to accelerate a reaction without being consumed in the reaction is crucial. Nevertheless, enzymes are transiently sequestered when they bind to their substrates; this sequestration limits activity and potentially compromises information processing and signal transduction. In this article, we analyse the mechanism of enzyme–substrate catalysis from the perspective of minimizing the load on the enzymes through sequestration, while maintaining at least a minimum reaction flux. In particular, we ask: which binding free energies of the enzyme–substrate and enzyme–product reaction intermediates minimize the fraction of enzymes sequestered in complexes, while sustaining a certain minimal flux? Under reasonable biophysical assumptions, we find that the optimal design will saturate the bound on the minimal flux and reflects a basic trade-off in catalytic operation. If both binding free energies are too high, there is low sequestration, but the effective progress of the reaction is hampered. If both binding free energies are too low, there is high sequestration, and the reaction flux may also be suppressed in extreme cases. The optimal binding free energies are therefore neither too high nor too low, but in fact moderate. Moreover, the optimal difference in substrate and product binding free energies, which contributes to the thermodynamic driving force of the reaction, is in general strongly constrained by the intrinsic free-energy difference between products and reactants. Both the strategies of using a negative binding free-energy difference to drive the catalyst-bound reaction forward and of using a positive binding free-energy difference to enhance detachment of the product are limited in their efficacy.
AU - Deshpande,A
AU - Ouldridge,T
DO - 10.1007/s00422-020-00846-6
EP - 668
PY - 2020///
SN - 0340-1200
SP - 653
TI - Optimizing enzymatic catalysts for rapid turnover of substrates with low enzyme sequestration
T2 - Biological Cybernetics: communication and control in organisms and automata
UR - http://dx.doi.org/10.1007/s00422-020-00846-6
UR - http://hdl.handle.net/10044/1/85338
VL - 114
ER -

logo

What's going on? Take a look at our events

Funders

Work in the IC-CSynB is supported by a wide range of Research Councils, Learned Societies, Charities and more.