Ginkgo Bioworks, the leading horizontal platform for cell programming, has recently adopted the Onyx platform into its foundries. The company was founded in 2008 with the mission to make biology easier to engineer. By leveraging high-throughput design and screening capabilities, they provide strain building services to other companies. For example, Ginkgo is developing plant probiotics for Joyn Bio, a joint venture with Leaps by Bayer, and producing rare natural ingredients for flavor and fragrance industry giant Givaudan. They have also partnered with Motif to make meat, dairy, and plant-based proteins in yeast strains at kilogram scale.
The Bioworks foundries integrate DNA synthesis, automation, and high-performance analytics. The Onyx platform fits well within the foundry’s workflow and was brought in to increase the performance and productivity of its metabolic and protein engineering efforts. The platform has already demonstrated order of magnitude increase in certain genome editing capabilities for S. cerevisiae and E. coli, and a 50% reduction in the design-build-test-learn times in an initial evaluation.
As a proof of work, the Onyx platform was used to increase the production of a small molecule in a previously engineered strain with 7 heterologous proteins. The project involved 3,000 modifications to the native E. coli gene expression and resulted in identifying 100 candidates for increased target molecule production. Ginkgo has highlighted these improvements in the ‘Our Work’ section of their website in a post titled ‘Ultra High Throughput Genome Engineering for the Production of Specialty Chemicals’. The full text is reposted below, with permission from Ginkgo Bioworks.
“Overview: Strain engineering often requires improving production hosts. In one such instance at Ginkgo, our team sought to modify our partner’s heavily-engineered E. coli strain. This strain already expressed 7 enzymes to produce their target molecule. One goal of this collaboration was to improve pathway productivity using genome-wide screening and engineering. This project leveraged several of Ginkgo’s capabilities, including DNA synthesis, strain construction, and ultra high-throughput screening.
The Ginkgo approach: Our campaign began by integrating multi-omics datasets. Our systems biology team used untargeted metabolomics to construct a metabolic model. We then used RNA-seq transcriptomics to identify differentially-expressed genes in the 0.25L Ambr 250 fermentation system. The data from this work, along with literature searches and Ginkgo’s in-house expertise, defined a set of more than 300 genes predicted to impact the production of the target small molecule.
Genome engineering on ginkgo’s platform: We designed more than 3,000 genome edits that modulate expression of native E. coli genes, and applied these to a previously-engineered production strain. These constructs were designed, synthesized, and strains were built using the Inscripta Onyx platform—a system we have previously used to demonstrate an order of magnitude increase in the throughput of certain genome editing capabilities for S. cerevisiae and E. coli. Individual colonies were isolated using an automated colony picker designed by kbiosystems, cultured using automated systems developed at Ginkgo, and screened using ultra high-throughput acoustic ejection mass spectrometry from SCIEX.
This workflow of designing, building, and testing hypotheses from primary data resulted in a total of 144,000 mass spectrometry data points and identified more than 100 candidate strains with significantly improved titers in small-scale cultures. The strains from this work are candidates for further screening in Ginkgo’s Ambr 250 fermentation system. This engineering campaign from design of DNA to generation of screening data was completed in approximately three months.
This case study is an example of how Ginkgo integrates automation, next-generation sequencing, digitized DNA design and strain construction, and ultra high-throughput chemical analytics into a single workflow. Our flexible platform allows the development of many types of workflows that stitch together the latest technologies and bring quick, effective metabolic engineering solutions for our customers.”