Protease circuits for processing biological information.
Protease circuits for processing biological information.
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DOI：
10.1038/s41467-020-18840-8
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发表时间：
2020-10-06
影响因子：
16.6
通讯作者：
Kwong GA
中科院分区：
文献类型：
--
作者：
Holt BA;Kwong GA
Engineered biocircuits designed with biological components have the capacity to expand and augment living functions. Here we demonstrate that proteases can be integrated into digital or analog biocircuits to process biological information. We first construct peptide-caged liposomes that treat protease activity as two-valued (i.e., signal is 0 or 1) operations to construct the biological equivalent of Boolean logic gates, comparators and analog-to-digital converters. We use these modules to assemble a cell-free biocircuit that can combine with bacteria-containing blood, quantify bacteria burden, and then calculate and unlock a selective drug dose. By contrast, we treat protease activity as multi-valued (i.e., signal is between 0 and 1) by controlling the degree to which a pool of enzymes is shared between two target substrates. We perform operations on these analog values by manipulating substrate concentrations and combine these operations to solve the mathematical problem Learning Parity with Noise (LPN). These results show that protease activity can be used to process biological information by binary Boolean logic, or as multi-valued analog signals under conditions where substrate resources are shared. In contrast to genetic circuits, here the authors develop protein biocircuits based on proteases. They show these activity-based circuits can execute Boolean logic for programmable drug delivery and perform fuzzy logic to solve a mathematical oracle problem, Learning Parity with Noise.
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影响因子：
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作者：
Donnelly S;Dalton JP;Robinson MW
通讯作者：
Robinson MW
影响因子：
5.4
作者：
Bulbake U;Doppalapudi S;Kommineni N;Khan W
通讯作者：
Khan W
影响因子：
17.1
作者：
Courbet, Alexis;Endy, Drew;Bonnet, Jerome
通讯作者：
Bonnet, Jerome
影响因子：
14.9
作者：
Fernandez-Rodriguez J;Voigt CA
通讯作者：
Voigt CA
影响因子：
17.1
作者：
Dudani JS;Jain PK;Kwong GA;Stevens KR;Bhatia SN
通讯作者：
Bhatia SN