Reference: Astolfi MCT, et al. (2025) Automated Strain Construction for Biosynthetic Pathway Screening in Yeast. ACS Synth Biol 14(10):4143-4151

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Abstract


Automation accelerates the Design-Build-Test-Learn (DBTL) cycle for synthetic biology; however, most strain construction pipelines lack robotic integration. Here, we present the workflow design and source code for a modular, integrated protocol that automates the Build step in Saccharomyces cerevisiae. We programmed the Hamilton Microlab VANTAGE to integrate off-deck hardware via its central robotic arm, enabling automated steps that increased throughput to 2,000 transformations per week. We developed a user interface with the Hamilton VENUS software to support on-demand parameter customization. As a proof of concept, we screened a gene library in an engineered yeast strain producing verazine, a key intermediate in the biosynthesis of steroidal alkaloids. Our pipeline rapidly identified pathway bottlenecks and genes that enhanced verazine production by 2.0- to 5-fold. This technical note provides resources for synthetic biologists designing yeast workflows for biofoundries to screen libraries for pathway discovery/optimization, combinatorial biosynthesis, and protein engineering.

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Journal Article
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Astolfi MCT, Yoder SD, Delfa-Lalaguna M, Winegar PH, Holm SKF, Lei M, Zhao X, Tan SE, Louie R, Hillson NJ, ... Show all
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