Ishtiaq Saaem1 2 3

1, The Foundry, Cambridge, Massachusetts, United States
2, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States
3, Synthetic Biology Center, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States

Centralized facilities for genetic engineering, or “biofoundries”, offer the potential to design organisms to address emerging needs in medicine, agriculture, industry, and defense. To date, by applying a diversity of new approaches, we have produced the desired molecule or material that has been asked by clients from the pharmaceutical and biotech industries as well as from the DOD. Specifically, we increased the titers of 1-hexadecanol, pyrrolnitrin, pacidamycin D, and clavulanic acid, found novel routes to the enediyne warhead underlying powerful antimicrobials, established a cell-free system for monoterpene production, and produced an intermediate toward vincristine biosynthesis. Furthermore, we have produced small-molecules linalool and phloroglucinol that, respectively, serve as precursors to JP-10 that fuels missiles and TATB that detonates the warheads. For materials production, we have encoded 7802 individually retrievable pathways to 540 bisindoles in a DNA pool, and created 61 biosynthetic capsaicin variants that could be central to high-performance polymers. In sum, we constructed several megabases of DNA, built hundreds of strains spanning six species (Saccharomyces cerevisiae, Escherichia coli, Streptomyces albidoflavus, Streptomyces coelicolor, Streptomyces clavuligerus and Streptomyces albovinaceus), established two cell-free systems, and performed nearly a thousand assays developed in-house for the molecules.