Translational control of enzyme scavenger expression with toxin-induced micro RNA switches.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Enzymes/*metabolism ; MicroRNAs/*genetics ; Protein Biosynthesis/*genetics ; Toxins, Biological/*toxicity; Base Sequence ; Cytochrome P-450 CYP1A2/metabolism ; Enzyme Activation/drug effects ; Gene Silencing ; HEK293 Cells ; Humans ; MicroRNAs/chemistry ; MicroRNAs/metabolism ; Nucleic Acid Conformation ; Theophylline/pharmacology ; Time Factors

Biological computation requires in vivo control of molecular behavior to progress development of autonomous devices. miRNA switches represent excellent, easily engineerable synthetic biology tools to achieve user-defined gene regulation. Here we present the construction of a synthetic network to implement detoxification functionality. We employed a modular design strategy by engineering toxin-induced control of an enzyme scavenger. Our miRNA switch results show moderate synthetic expression control over a biologically active detoxification enzyme molecule, using an established design protocol. However, following a new design approach, we demonstrated an evolutionarily designed miRNA switch to more effectively activate enzyme activity than synthetically designed versions, allowing markedly improved extrinsic user-defined control with a toxin as inducer. Our straightforward new design approach is simple to implement and uses easily accessible web-based databases and prediction tools. The ability to exert control of toxicity demonstrates potential for modular detoxification systems that provide a pathway to new therapeutic and biocomputing applications.

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0 (Enzymes)
0 (MicroRNAs)
0 (Toxins, Biological)
C137DTR5RG (Theophylline)
EC 1.14.14.1 (Cytochrome P-450 CYP1A2)

Date Created: 20210129 Date Completed: 20210916 Latest Revision: 20210916

20250114

PMC7844233

10.1038/s41598-021-81679-6

33510250