1.
Biotechnological production of alpha-keto acids: Current status and perspectives.
Song, Y, Li, J, Shin, HD, Liu, L, Du, G, Chen, J
Bioresource technology. 2016;:716-724
Abstract
Alpha-keto (α-keto) acids are used widely in feeds, food additives, pharmaceuticals, and in chemical synthesis processes. Although most α-keto acids are currently produced by chemical synthesis, their biotechnological production from renewable carbohydrates is a promising new approach. In this mini-review, we first present the different types of α-keto acids as well as their applications; next, we summarize the recent progresses in the biotechnological production of some important α-keto acids; namely, pyruvate, α-ketoglutarate, α-ketoisovalerate, α-ketoisocaproate, phenylpyruvate, α-keto-γ-methylthiobutyrate, and 2,5-diketo-d-gluconate. Finally, we discuss the future prospects as well as favorable directions for the biotechnological production of keto acids that ultimately would be more environment-friendly and simpler compared with the production by chemical synthesis.
2.
Recent advances in microbial production of δ-aminolevulinic acid and vitamin B12.
Kang, Z, Zhang, J, Zhou, J, Qi, Q, Du, G, Chen, J
Biotechnology advances. 2012;(6):1533-42
Abstract
δ-aminolevulinate (ALA) is an important intermediate involved in tetrapyrrole synthesis (precursor for vitamin B12, chlorophyll and heme) in vivo. It has been widely applied in agriculture and medicine. On account of many disadvantages of its chemical synthesis, microbial production of ALA has been received much attention as an alternative because of less expensive raw materials, low pollution, and high productivity. Vitamin B12, one of ALA derivatives, which plays a vital role in prevention of anaemia has also attracted intensive works. In this review, recent advances on the production of ALA and vitamin B12 with novel approaches such as whole-cell enzyme-transformation and metabolic engineering are described. Furthermore, the direction for future research and perspective are also summarized.
3.
A systems approach to plant bioprocess optimization.
Cloutier, M, Chen, J, De Dobbeleer, C, Perrier, M, Jolicoeur, M
Plant biotechnology journal. 2009;(9):939-51
Abstract
A dynamic model for plant cell metabolism was used as a basis for a rational analysis of plant production potential in in vitro cultures. The model was calibrated with data from 3-L bioreactor cultures. A dynamic sensitivity analysis framework was developed to analyse the response curves of secondary metabolite production to metabolic and medium perturbations. Simulation results suggest that a straightforward engineering of cell metabolism or medium composition might only have a limited effect on productivity. To circumvent the problem of the dynamic allocation of resources between growth and production pathways, the sensitivity analysis framework was used to assess the effect of stabilizing intracellular nutrient concentrations. Simulations showed that a stabilization of intracellular glucose and nitrogen reserves could lead to a 116% increase in the specific production of secondary metabolites compared with standard culture protocol. This culture strategy was implemented experimentally using a perfusion bioreactor. To stabilize intracellular concentrations, adaptive medium feeding was performed using model mass balances and estimations. This allowed for a completely automated culture, with controlled conditions and pre-defined decision making algorithm. The proposed culture strategy leads to a 73% increase in specific production and a 129% increase in total production, as compared with a standard batch culture protocol. The sensitivity analysis on a mathematical model of plant metabolism thus allowed producing new insights on the links between intracellular nutritional management and cell productivity. The experimental implementation was also a significant improvement on current plant bioprocess strategies.