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. Author manuscript; available in PMC: 2021 Jun 19.
Published in final edited form as: ACS Synth Biol. 2020 May 12;9(6):1270–1276. doi: 10.1021/acssynbio.0c00135

Figure 1.

Figure 1.

Automated Continuous Evolution (ACE). (a) OrthoRep enables continuous diversification of genes of interest (GOIs) via in vivo targeted mutagenesis in yeast. The basis of OrthoRep is an orthogonal DNA polymerase-plasmid pair that mutates GOIs ~100,000-fold faster than the genome. (b) eVOLVER is a continuous culturing platform for programmable, multiparameter control of selection conditions across many independent cultures. A PID control algorithm implemented with eVOLVER dynamically tunes selection pressure of populations as they adapt, precisely challenging them to achieve desired functions. PID control is achieved by tuning the ratio of full selection and no selection media inputs in response to growth rate. (c) By running OrthoRep in eVOLVER with PID control, ACE autonomously and rapidly navigates complex fitness landscapes. With a single framework, ACE can guide independent cultures through diverse trajectories.