Bioprocess scale-up through experimental design and process simulation: a case study of succinic acid and 3-hydroxypropionic acid

Abstract

The bioprocess scale-up is at the center when developing an upstream process for mass production [1]. Process understanding at the laboratory scale can guide the scale-up rules [2-4]. These rules are broadly classified into maintaining (1) the same mixing time, (2) constant power supplied per unit volume (P/V), (3) constant overall mass transfer coefficient (kLa), and (4) impeller flow numbers [3,4]. Accordingly, different scale-up correlations have been derived and are functions of impeller Reynolds number (Re), impeller tip speed, power transfer per unit volume, and agitation rate [2-4]. At different scales, this correlation-based scale-up can produce comparable biomass [4 and 5].

Thus, in the process of SA mass-production via fermentation, different studies have attempted to scale up fermentative succinic acid (SA) production via yeast. In one study, from an engineered Yarrowia lipolytica PSA02004 via two-stage pH regulation between 5-6 in fed-batch mode a SA titer value of 42.2 g.L-1 with 0.38 g.g-1 yield and 0.84 g.L-1.h-1 productivity is obtained [6]. In the same study, the shake flask scale is translated to the lab-scale reactor at 6.7 L (Working volume: 3L) [7]. Another study in batch mode resulted in an SA titer of 18.4 g.L-1 with a yield of 0.23 g.g-1 at pH 3.0. However, in fed-batch mode, with seven-time feeding, a higher titer value of 76.8 g.L-1 is achieved. The study utilizes an in situ fibrous bed bioreactor (isFBB) of volume 2.5 L [8]. In other studies, via batch or fed-batch mode with multiple feeding mostly near pH 6, the SA values titer and yield in the range of 53.6 g.L-1-209.7 g.L-1 and 0.92 g.g-1 are reported, respectively [9, 10]. However, almost all these studies are limited either to shake flask or to the bioreactor total volume in the range of 1-10 L [6-10].