2025 AIChE Annual Meeting

(344c) Bioprocess Scale-up through Experimental Design and Process Simulation: Case in Point Succinic Acid and 3-Hydroxy Propionic Acid

Authors

Somesh Mishra - Presenter, IIT Delhi, India
Vijay Singh, University of Illinois at Urbana-Champaign
Huimin Zhao, University of Illinois-Urbana
Anurag Rathore, Amgen Inc.
Smita Raghuvanshi, Birla Institute of Technology and Science (BITS) - BITS Pilani, Pilani Campus, Rajasthan, India
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].

Previously, our batch fermentation using sugarcane juice medium in a pilot-scale fermenter (300×) resulted in 63.1 g.L-1 of SA with a Space-time yield (STY) value of 0.66 g.L-1.h-1. However, limited Studies are available on low-pH fermentation to produce SA via yeast at higher scales of 75L. Also, during scale-up, the application of engineering criteria is neglected, which results in process failure on scale-up. The pilot-scale plant data and operational understanding can improve large-scale plant design and performance.

Here, we report a truly competitive precision fermentation-based SA production at an industrially relevant scale (3000x). Our results indicate STY, yield and titer values of 0.96 g.L-1.h-1, 0.8 g SA per g of dextrose and 78.37 g.L-1, respectively. The investigation identifies how the selection of feedstock, growth medium, and sensible CO2 can make SA mass production profitable.

References

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