Defining the scope of opportunities and risks in biosynthetic chemical production using the Act Synthesizer

View all posters

Saurabh Srivastava, Tim Hsiau, Paul Ruan, Jeff Tsui, Sarah Chasins, Jene Li, Sanjit A. Seshia, Rastislav Bodik, J. Christopher Anderson.

UC Berkeley, United States

We present here the Act Ontology and pathway inference tool, the Act Synthesizer. The Act Ontology formalizes and stores biochemical function knowledge in an extensible and uniform manner. We populate the Act ontology by aggregating enzymatic data across various sources and deriving biochemical rules from them. We use the ontology as the underlying framework for the Act Synthesizer tool that, when provided a natural or unnatural chemical target, generates a plausible enzymatic pathway to the target. We have used the tool’s predictions to design and test E. coli strains to establish the reliability of our tool. The Act Synthesizer allows users to comprehensively survey the space of observed enzymatic reactions in several ways; a user can ask whether a chemical can be made from known reactions, they can identify all alternate pathways to a desired target chemical, and they can compute the list of chemicals that can plausibly be made in cells. We have the ability to predict, at least as a conservative over-approximation, what can be done in the space of microbial chemical factories. This enables our community to anticipate potentially dangerous constructs prior to release of tools with public access, and proactively intervene to avoid unintentional production of dangerous organisms.