2025 AIChE Annual Meeting

(595d) Model-Based Optimization of Fermentation Strategy for Cost-Effective Production of O-Acetyl-L-Homoserine

Authors

Dami Kim, Chungnam national university
Hongbum Choi, Korea Advanced Institute of Science and Technology
Jay Hyung Lee, University of Southern California
Jung-Ho Kim, CJ CheilJedang Corp.
Dong-Hun Kwak, CJ CheilJedang Corp.
Joseph Kwon, Texas A&M University
Kosan Roh, Korea Advanced Institute of Science and Technology (KAIST)
O-acetyl-L-homoserine (OAH) is a key biochemical intermediate as a direct precursor to L-methionine, the principal sulfur-containing amino acid in proteins. It can be produced via aerobic microbial fermentation using engineered strains. Sucrose is often used as a single-carbon source for the production of OAH; however, we introduce a novel dual-carbon strategy incorporating acetic acid as a secondary carbon source. This approach aims to reduce raw material costs and also facilitate the recycling of industrial byproducts. A key challenge lies in achieving an optimal trade-off between cost and productivity, which requires optimization of critical operational parameters—such as substrate concentration and feeding rate. Model-based strategies have been extensively validated in prior studies as effective tools to enhance both productivity and economic efficiency.[01,02]

In this study, we develop a mathematical model of aerobic fed-batch fermentation for OAH production using Corynebacterium to derive an optimal feeding strategy. The process begins with a batch phase in a 30 L bioreactor, followed by a fed-batch phase using a single-feed system delivering sucrose and acetic acid. We first tested various feed concentration profiles experimentally. Based on the experimental data, we construct a kinetic model to predict the dynamic behavior of the fermentation. Key parameters are initially estimated using the Monod model [03], followed by a modified Luong-type model [04] to account for substrate inhibition under excess substrate concentrations. Simulation results indicate that maintaining substrate concentrations between the saturation constant (Ks) and inhibition constant (Kis) enhances productivity and thus lowers production costs. Optimization of the feeding rate and concentration profile during the fed-batch phase is then carried out to further minimize the cost of OAH production. This study presents a systematic framework that combines sequential kinetic modeling and process optimization, offering practical insights for the economically viable and scalable production of OAH in industrial fermentation.

Reference

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2. Shah, P., Sheriff, M. Z., Bangi, M. S. F., Kravaris, C., Kwon, J. S., Botre, C., & Hirota, J. (2022). Multi‐rate observer design and optimal control to maximize productivity of an industry‐scale fermentation process. AIChE Journal, 69(2).

3. Monod, J. (1949). The growth of bacterial cultures. Annual Review of Microbiology, 3(1), 371–394.

4. Luong, J. H. T. (1987). Generalization of monod kinetics for analysis of growth data with substrate inhibition. Biotechnology and Bioengineering, 29(2), 242–248.