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Enabling complex genetic circuits to respond to extrinsic environmental signals
Author(s) -
HoynesO'Connor Allison,
Shopera Tatenda,
Hinman Kristina,
Creamer John Philip,
Moon Tae Seok
Publication year - 2017
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.26279
Subject(s) - nand gate , synthetic biology , electronic circuit , nand logic , computer science , logic gate , construct (python library) , metabolic engineering , set (abstract data type) , computational biology , biology , engineering , genetics , electrical engineering , gene , algorithm , programming language
Genetic circuits have the potential to improve a broad range of metabolic engineering processes and address a variety of medical and environmental challenges. However, in order to engineer genetic circuits that can meet the needs of these real‐world applications, genetic sensors that respond to relevant extrinsic and intrinsic signals must be implemented in complex genetic circuits. In this work, we construct the first AND and NAND gates that respond to temperature and pH, two signals that have relevance in a variety of real‐world applications. A previously identified pH‐responsive promoter and a temperature‐responsive promoter were extracted from the E. coli genome, characterized, and modified to suit the needs of the genetic circuits. These promoters were combined with components of the type III secretion system in Salmonella typhimurium and used to construct a set of AND gates with up to 23‐fold change. Next, an antisense RNA was integrated into the circuit architecture to invert the logic of the AND gate and generate a set of NAND gates with up to 1168‐fold change. These circuits provide the first demonstration of complex pH‐ and temperature‐responsive genetic circuits, and lay the groundwork for the use of similar circuits in real‐world applications. Biotechnol. Bioeng. 2017;114: 1626–1631. © 2017 Wiley Periodicals, Inc.