Fermentation development titer improvement

Starting with bench scale equipment (up to 100 L in the so-called kilo lab) or pilot scale fermentors (up to 5000 L when titer is low), this early preparative work uses whatever synthetic method or fermentation conditions (the microorganism and the nutrients) are immediately available. In most cases of synthesis, the route may be a somewhat streamlined version of the discovery route or a temporary route that may or may not include parts of synthesis schemes being considered for eventual development. In most cases of biosynthesis, the microorganism is that from the discovery stage, but taken from whatever stage of microbial strain improvement is amenable to scale up from shake flasks or bench scale fermentors. 

Very recently, a further improved yeast system was reported, which induded, among other optimizations and besides CYP71AV1, an alcohol and aldehyde [119] dehydrogenases (ADHl and ALDHl) from A. annua for artemisinic alcohol and aldehyde conversion, respectively (Scheme 5.28). Artemisinic acid titers of up to 25gl i were achieved in fermentation set-up [120]. A process based on the developed artemisinic acid-producing yeast strain is now used for the industrial production of artemisinin at Sanofi (www.rsc.org/chemistryworld/2013/04/sanqfi-launches-malaria-drug-production). 

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