Building New Pathways

Overview

The Foundry’s enzyme discovery, pathway assembly, and high-throughput analytical capabilities enable organism engineers to build complex metabolic pathways in microorganisms. These pathways are designed to produce cultured ingredients, break down materials, and improve performance of strains.

Case Study Image

Case Study

A leading company in the field of industrial fermentation wished to significantly decrease their reliance on expensive industrial feedstocks, replacing it with a low-cost substrate that the strain could not naturally assimilate. Ginkgo was tasked with engineering a complex metabolic pathway into the strain, then fine-tuning the strain to maintain the original yield at lower cost.

Foundry Approach Image

Foundry Approach

The project required the synthesis, screening, and improvement of thousand-member enzyme libraries and the assembly of flux-balanced pathways to reroute carbon equivalents toward the specific product of interest. While traditional, bench-based metabolic engineering teams may have approached this challenge with large research groups working for many years, this project was completed at Ginkgo in 24 months by two full time organism engineers using the Ginkgo Foundries.

Overall, Ginkgo leveraged its capabilities in DNA synthesis and high-throughput screening to synthesize 109 million base pairs of DNA, screen 7117 enzymes belonging to 12 enzyme classes, and evaluate 2719 pathways, for a total of 30,445 strain tests.

Result Image

Result

After finding the genes expressing the most active enzymes and combining them with a library of Ginkgo-verified regulatory parts, we assembled the pathway in Ginkgo’s Foundry. By the conclusion of the project, the strain could assimilate the new feedback nearly 25 times more than the original strain.

Scaling down the size of each experiment enables Ginkgo’s organism engineers to automate strain construction at high-throughput.