RT Journal Article SR Electronic T1 A Synthetic Microbial Operational Amplifier JF bioRxiv FD Cold Spring Harbor Laboratory SP 161828 DO 10.1101/161828 A1 Ji Zeng A1 Jaewook Kim A1 Areen Banerjee A1 Rahul Sarpeshkar YR 2017 UL http://biorxiv.org/content/early/2017/07/10/161828.abstract AB Synthetic biology has created oscillators, latches, logic gates, logarithmically linear circuits, and load drivers that have electronic analogs in living cells. The ubiquitous operational amplifier, which allows circuits to operate robustly and precisely has not been built with bio-molecular parts. As in electronics, a biological operational-amplifier could greatly improve the predictability of circuits despite noise and variability, a problem that all cellular circuits face. Here, we show how to create a synthetic 3-stage inducer-input operational amplifier with a differential transcription-factor stage, a CRISPR-based push-pull stage, and an enzymatic output stage with just 5 proteins including dCas9. Our ‘Bio-OpAmp’ expands the toolkit of fundamental circuits available to bioengineers or biologists, and may shed insight into biological systems that require robust and precise molecular homeostasis and regulation.One Sentence Summary A synthetic bio-molecular operational amplifier that can enable robust, precise, and programmable homeostasis and regulation in living cells with just 5 protein parts is described.