Over my 40+ year career in industrial biotechnology, I’ve parcipated in quite a few fermentaon projects, including several rst-of-a-kind, totaling over a billion investment dollars. These projects had widely varying outcomes, ranging from miserable failure to great success. The rst ones coincided with the early days of metabolic engineering and the last with emerging synthec biology. Along the way, I like to think I’ve learned a thing or two - oen the hard way. In recent years, I’ve shared as much as possible - the good, the bad, and the ugly - through publicaons, presentaons, short courses, workshops, conferences, and consulng. Two case studies will be presented, both involving transfer of developed processes to manufacturing plants. The rst was a costly, painful failure: the conversion of an acve citric acid facility to astaxanthin producon. The second was a remarkable success: the conversion of a mothballed amino acids facility to 1,4-butanediol producon. Three basic principles were inspired by all of this: 1) begin with the end in mind; 2) mind the details; and 3) prepare for the unexpected.

dsm-firmenich is a purpose-led, performance-based leader in fragrance, taste, health, nutrition, and bioscience. We harness biology to create brighter lives for all and a sustainable future. Effective use of predictive models is essential for developing disruptive bioprocess platforms that deliver sustainable and profitable performance at scale. At dsm-firmenich we make use of multiple metabolic modeling paradigms in a fit-for-purpose approach to guide strain engineering, process development, continuous improvement, and to inform technoeconomic and lifecycle analyses. At the heart each methodology is a genome-scale description of metabolism. Central to our philosophy is democratization of model use to maximize impact. As we move towards net-zero processing, user-friendly and flexible models of metabolism become essential for derisking investment, allowing us to benchmark experiments against theoretical limits and understand simultaneously the metabolic and economic implications of transitioning our processes to sustainable feedstocks.