Clean manufacturing powered by biology: how Amyris has deployed technology and aims to do it better
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FERMENTATION, CELL CULTURE AND BIOENGINEERING - ORIGINAL PAPER
Clean manufacturing powered by biology: how Amyris has deployed technology and aims to do it better Paul Hill1 · Kirsten Benjamin1 · Binita Bhattacharjee1 · Fernando Garcia1 · Joshua Leng1 · Chi‑Li Liu1 · Abhishek Murarka1 · Douglas Pitera1 · Elisa Maria Rodriguez Porcel1 · Iris da Silva2 · Chuck Kraft1 Received: 30 June 2020 / Accepted: 17 September 2020 © The Author(s) 2020
Abstract Amyris is a fermentation product company that leverages synthetic biology and has been bringing novel fermentation products to the market since 2009. Driven by breakthroughs in genome editing, strain construction and testing, analytics, automation, data science, and process development, Amyris has commercialized nine separate fermentation products over the last decade. This has been accomplished by partnering with the teams at 17 different manufacturing sites around the world. This paper begins with the technology that drives Amyris, describes some key lessons learned from early scale-up experiences, and summarizes the technology transfer procedures and systems that have been built to enable moving more products to market faster. Finally, the breadth of the Amyris product portfolio continues to expand; thus the steps being taken to overcome current challenges (e.g. automated strain engineering can now outpace the rest of the product commercialization timeline) are described. Keywords Technology transfer · Fermentation · Farnesene · Scale-up · Amyris
Introduction Amyris is a fermentation product company that leverages synthetic biology and has been bringing novel fermentation products to the market since 2009. Founded in 2003 to create a reliable supply of cost-effective artemisinin for the treatment of malaria, Amyris has now scaled up and manufactured nine distinct fermentation molecules (terpenoids like farnesene, manool, bisabolol; terpenoid-based species like RebM; and non-terpenoid products) with multiple contract manufacturing organization (CMO) partners around the world. The foundation of that achievement is an investment of > $500 M in building powerful Research and Development (R&D) capabilities—essentially industrializing the design/build/test paradigm, enabling orders of magnitude increases in the rate of strain generation and testing, * Paul Hill [email protected] 1
Amyris, Inc., 5885 Hollis Street, Ste. 100, Emeryville, CA 94608, USA
Amyris Brasil Ltda., Rua John Dalton, 301‑Bloco B‑Edificio 3, Condominio Techno Plaza, Campinas, SP 13069‑330, Brazil
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significantly improving the quality of the strain construction, and building data systems to accelerate learning. Additionally, significant technical innovations have helped to ensure that these strains succeed in the commercial fermentation environment. For example, Amyris strain engineers have pioneered the reprogramming of central metabolism to significantly improve product yields and metabolic rates [1]. Simple, proprietary, and robust genetic switches have been developed which preserve cellul
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