Fluxomic analysis of central carbon metabolism in Actinobacillus succinogenes using chemostat cultures

Succinic acid is an essential platform chemical for several industries including polymer, food, and pharmaceutical. However, production of succinic acid from petrochemical resources is harmful for the environment, and its production cost is highly dependent on the luctuating oil prices. Bio-based production is sustainable and environmentally benign, but still requires process development to be economically competitive to petrochemical route. Actinobacillus succinogenes is a natural succinic acid producer with high yields, and also a well-studied microorganism. Its capability to consume a variety of carbon sources makes it possible to work on novel substrates. Delactosed whey permeate is a waste product of dairy industry, still rich in lactose, salts, and minerals, additionally containing organic acids. This work evaluates it as a substrate for fermentative succinic acid production. Fermentation characteristics of A. succinogenes were studied in batch fermentations with synthetic media, and then delactosed whey permeate was successfully used as a substrate in batch and chemostat cultures for succinic acid production. Growth and non-growth associated energy needs of the microorganism were estimated on different substrates based on the fermentation data. Flux balance analysis is carried using available metabolic model to determine the flow of carbon within primary metabolism, to quantify the capnophilic activity, and to simulate the metabolism for different production scenarios.