Extending Amyris' Genotype Specification Language (GSL) for Modular and Combinatorial Genome Engineering

As synthetic biologists continue to push the boundaries of genome engineering techniques and strategies, the infrastructure to implement these new strategies must similarly expand. Although individual engineers have been able to produce beautiful artisanal constructs using direct DNA editing techniques, they cost significant time to intricately align raw sequences and are thus error-prone and unscalable. These shortcomings have led to the development of a host of Computer Aided Design (CAD) tools to enable engineers to more efficiently engineer genomes. These CAD tools have ranged from symbolic drag-and-drop interfaces to text-based language tools, often with the goal of moving users away from editing raw DNA and towards more general and reusable genetic elements. Genotype Specification Language (GSL) is an instance of a language-based genome engineering tool that has been developed and tested within Amyris’ strain design platform for the past 6 years, and has recently been made available as open source. GSL balances the needs for quick and efficient design creation against the needs for design complexity and specificity; it abstracts functional genetic parts—such as gene, promoter, terminator, and homology parts—into a simple syntax while providing precision editing syntax to allow users to manipulate the sequences within these parts. Although GSL’s code-like interface may feel most natural to those with some background in programming, its syntax style was intentionally designed to reflect notational conventions from genetics, which has facilitated easier adoption of the language among biologists as well. Today, as Amyris’ pipeline expands to include the rapid and parallel scale up of hundreds of molecules, so too has GSL’s syntax expanded to include new features such as variables and functions. During initial testing, these features have enabled easier specification of modular and combinatorial designs and in turn have improved engineers’ ability to submit high-quality suites of designs to Amyris’ Automated Strain Engineering service for construction.