1.3- Propanediol metabolic engineering

It is important that chemical engineers master an understanding of metabolic engineering, which uses genetically modified or selected organisms to manipulate the biochemical pathways in a cell to produce a new product, to eliminate unwanted reactions, or to increase the yield of a desired product. Mathematical models have the potential to enable major advances in metabolic control. An excellent example of industrial application of metabolic engineering is the DuPont process for the conversion of com sugar into 1,3-propanediol,... 

Hydroxypropionic Acid (3-HPA). Like the structurally isomeric lactic acid, 3-HPA constitutes a three-carbon building block with the potential of becoming a key intermediate for a variety of high-volume chemicals malonic and acrylic acids, methacrylate, acrylonitrile, 1,3-propanediol, and so forth.Thus, Cargill is developing a low-cost fermentation route by metabolic engineering of the microbial... 

Zhu, M. M. Lawman, P. D. Cameron, D. C. Improving 1,3-propanediol production from glycerol in a metabolically engineered E.coli by reducing accumulation of glycerol-3-phosphate, Biotechnol. Prog., 2002, 18, 694-699. 

Altaras, N. E. Cameron, D. C. Metabolic engineering of a 1,2-propanediol pathway in E.coli, Appl. Environ. Microbiol., 1999, 65, 1180-1185. (b) Enhanced production of... 

Several important examples of metabolic engineering, ranging from applications in basic chemicals, such as the manufacture of propanediol from glucose, to the synthesis of chiral pharmaceutical intermediates, such as (2i )-indanediol, a building block of the HIV protease inhibitor Crixivan (Indinavir , Merck see Chapter 13, Section 13.3.3.30.), are presented in Chapter 20. 

Nakamura, C. and Whited, G., Metabolic engineering for the microbial production of 1,3 propanediol. Curr Opin... 

There are already several examples of chemicals being produced by microbial fermentation of engineered cell factories, whose production through metabolic engineering has been boosted by the use of genomics tools, e.g., 1,3-propanediol used for polymer production, riboflavin used as a vitamin, and 7-aminodeacetoxy-cephalosporanic acid (7-ADCA) used as a precursor for antibiotics production. Furthermore, in the quest to develop a more sustainable society, the chemical industry is currently developing novel processes for many other fuels and chemicals, e.g., butanol, to be used for fuels, organic acids to be used for polymer production, and amino acids to be used as feed. 

Amino acids, citric acid, lactic acid, propanediol, penicillin G, synthetic drug intermediates, and therapeutic proteins are among the industrially relevant products of fermentation and cell culture that have been targets for metabolic engineering. Some ofthis work has been adopted by industry (see [72], section 16.4.1). The major aim was to optimize the yields of industrial products, which was efficiently realized with Corynebacterium glutamicum for lysine and tryptophan, and at the Dupont company for 1,3-propane diol production [107-109]. 

Metabolic engineering of a 1, 2-propanediol pathway in Escherichia coli. Appl. Environ. Microbiol, 65, 1180-1185. 

Niimi, S., Suzuki, N., Inui, M., and Yukawa, H. (2011) Metabolic engineering of 1,2-propanediol pathways in Corynebacterium glutamicum. 

Boenigk R, Bowien S, Gottschalk G (1993) Fermentation of glycerol to PDO in continuous cultures of Citrobacter freundii. Appl Microbiol Biotechnol 38 453-457 Cameron DC, Altaras NE, Hoffman ML (1998) Metabolic engineering of propanediol pathways. Biotechnol Progr 14(116) 125... 

Cameron DC, Altaras NE, Hoffman ML, Shaw AJ. (1998). Metabolic engineering of propanediol pathways. Biotechnol Prog, 14,116-125. 

Celinska E. (2012). Klebsiella spp as a 1,3-propanediol producer—the metabolic engineering approach. Grit Rev Biotechnol, 32, 274—288. 

Gonzalez-Pajuelo M, Meynial-Salles I, Mendes F, Andrade JC, Vasconcelos I, Soucaille P. (2005b). Metabolic engineering of Clostridium acetobutylicum for the industrial production of 1,3-propanediol from glycerol. Metab Eng, 1, 329-336. 

The industrial focus on 1,3-propanediol has sparked interest in the microbial production of 1,2-propanediol. Some work has focused on the fermentation process of 1,2-propanediol as well as the metabolic engineering of pathways for its production. In early work with C. thermosaccharolyticum, various process conditions were examined such as temperature, pH, gas phase composition, and substrate concentration. This work was conducted in a volume of 2 1. The maximum cell concentration achieved was in the range of 1.0-1.3 g/1. The temperature range examined was 50-65 °C, and the optimal temperature for production was 60 °C. At higher temperatures, lactate decreased and ethanol increased. The pH range studied was from 6.0 to 7.2. At the optimal pH of 6.0, a concentration of 5.6 g/1 of 1,2-PD was obtained. Other fermentation conditions were examined such as... 

Cameron DC, Tong IT, Skraly FA (1993) Metabolic engineering for the production of 1,3-propanediol. In Chianelli RR, Davison BH (eds) ACS symposium on bioremediation and bioproAmerican Chemical Society, Denver CO, pp 294-295... 

One of the first biobased products being commercialized exemplifying the promise of combining metabolic engineering with advanced process design to achieve a sustainable product with superior properties at a low cost is biobased 1,3-propanediol (PDO). Because biobased PDO is not yet produced in commercial quantities, this is a good time to take early measure of how well die biobased pathway meets the objectives of sustainable and environmentally benign production. 

Nakamura, C. Production of 1,3-propanediol by E. coli presented at Metabolic Engineering IV Applied System Biology, II Ciocco, Castelvecchio Pascoli, Italy, October 8,2002. 

---