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Biomimicry Promotes the Efficiency of a 10‐Step Sequential Enzymatic Reaction on Nanoparticles, Converting Glucose to Lactate

For nanobiotechnology to achieve its potential, complex organic–inorganic systems must grow to utilize the sequential functions of multiple biological components. Critical challenges exist: immobilizing enzymes can block substrate‐binding sites or prohibit conformational changes, substrate compositi...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2017-01, Vol.56 (1), p.235-238
Main Authors: Mukai, Chinatsu, Gao, Lizeng, Nelson, Jacquelyn L., Lata, James P., Cohen, Roy, Wu, Lauren, Hinchman, Meleana M., Bergkvist, Magnus, Sherwood, Robert W., Zhang, Sheng, Travis, Alexander J.
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Language:English
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Summary:For nanobiotechnology to achieve its potential, complex organic–inorganic systems must grow to utilize the sequential functions of multiple biological components. Critical challenges exist: immobilizing enzymes can block substrate‐binding sites or prohibit conformational changes, substrate composition can interfere with activity, and multistep reactions risk diffusion of intermediates. As a result, the most complex tethered reaction reported involves only 3 enzymes. Inspired by the oriented immobilization of glycolytic enzymes on the fibrous sheath of mammalian sperm, here we show a complex reaction of 10 enzymes tethered to nanoparticles. Although individual enzyme efficiency was higher in solution, the efficacy of the 10‐step pathway measured by conversion of glucose to lactate was significantly higher when tethered. To our knowledge, this is the most complex organic–inorganic system described, and it shows that tethered, multi‐step biological pathways can be reconstituted in hybrid systems to carry out functions such as energy production or delivery of molecular cargo. Inspired by the sperm tail, a system of 10 glycolytic enzymes tethered via oriented immobilization to nanoparticles was developed. The efficiency of sequential tethered reactions to convert glucose to lactate was significantly higher than that of enzymes in solution. The results provide proof of principle that complex biological pathways can be reproduced in hybrid organic–inorganic systems.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201609495