Abstract
For the past 80–90 years petroleum and natural gas have served as raw materials for the majority of the finished products of our daily lives. After World War II these raw materials decisively substituted coal, and they have been the foundation of an enormous increase in material wealth and welfare throughout the World.
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- 1.
Older references such as Maiorella et al. (1984) should, however, not be neglected. This seminal paper has recently been honored by being reprinted in Biotechnol Bioeng (2009).
- 2.
- 3.
Although CO2 is obviously a metabolic product we shall use “lost carbon” (“lost” for further metabolism) for this compound.
- 4.
In figures we usually show the non-dissociated metabolites. At the pH at which most fermentations take place we have the anions: pyruvate, acetate, glutamate, CH3COCOO−, CH3COO−, etc. rather than the free acids. NH3 occurs as NH +4 . When we write stoichiometries (e.g., (2.1)) it is simpler to use the non-dissociated molecules. The need to add acid or base to keep the desired pH is implicitly assumed. In Chap. 4 the ionic forms will have to be used.
- 5.
Metabolism is full of surprises: Lengeler et al. (1999, p. 285) describes the anaerobic metabolism of glucose by to three HAc + four ATP. What happens is that CO2 from decarboxylation of pyruvate is reduced to Acetyl-P using the two NADH created in the EMP pathway.
- 6.
To save space in writing the stoichiometries only the reduced form of the redox carrier and the activated form (ATP) of the energy carrier are shown in this chapter. H2O is generally left out. The stoichiometric coefficient for H2O can be found from an O and an H balance (see Chap. 3).
- 7.
There are actually two cytosolic enzymes coded by different genes, GDPH1 and GDPH2. One enzyme is concerned with redox regulation in the cell whereas the other gives osmotolerance to the yeast when it grows in high salt concentrations (or at very high glucose concentration, e.g., in wine making). The glycerol production at the expense of some ethanol and biomass increases the quality of many wines, and yeast with overexpression of the gene is used by some winemakers (Remize et al. 1999). In the present text we are only concerned with the redox regulation role of GDPH to counteract the production of less reduced metabolic products, especially succinic acid, and the production of NADH when glucose is converted to biomass.
- 8.
Note in Fig. 2.7 that there are two forms of isocitrate dehydrogenase. One form which is located only in the mitochondria uses NAD+ as cofactor, the other is located both in the cytosol and in the mitochondria, and it uses NADP+ as cofactor. Equation (2.16) is written for the first form and holds for yeast, while bacteria must operate with the NADP+ requiring cytosolic enzyme. In fact this becomes an advantage when we produce, e.g., amino acids in bacteria, since the NADPH obtained in reaction (4) in Fig. 2.7 is needed in the biosynthesis of the amino acid (see Sect. 2.4).
- 9.
In a very interesting process Hols et al. (1999) have used genetic engineering to convert a homo(lactic)fermenting Lactococcus lactis to become a homo(alanine) fermenting organism. Since alanine has a much higher sales price than lactic acid this is a splendid idea. The paper does, however, show that very high NH3 concentrations are needed.
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Problems
Problems
Problem 2.1
A number of process designs for large-scale production of ethanol are available on the net. IOGEN, DONG-Inbicon, a Danisco-DuPont scheme, supported by U. Tennessee and several others can be found. Make an analysis of the different schemes. What products are made? What is the saccharification process? How well are down-stream processes designed with respect to total energy minimization?
What is the current market price for ethanol in bulk, and how well does it match the production cost of ethanol from lignocellulosic biomass?
References: Lynd et al. (2008), Lin and Tanaka (2006), Sendich et al. (2008), and also material from the biotech companies Novozymes and Genencor.
Problem 2.2
Consult the literature to find profiles for batch cofermentation of glucose and xylose by a “wild-type” yeast strain S. cerevisiae, and also by better yeast strains. Observe the sequential utilization of the sugars.
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How has S. cerevisiae been engineered in the group of Hahn-Hägerdahl to obtain a more rapid conversion of xylose? Describe the redox reactions used and comment on the difficulties of the process.
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2.
Compare the process of (1) with that of the Delft group of scientists (Wesselink et al. 2009).
Problem 2.3
Butanol (1-butanol, and perhaps even better iso-butanol) can become an excellent transportation fuel.
On the net you will find many recent proposals for the production of butanol by fermentation (e.g., a huge project by BP and DuPont). Give an account of the advantages of producing butanol rather than ethanol, and also outline some of the disadvantages.
Several papers from 2007/2009 review the biosynthesis of butanol: Lee et al. (2008), Atsumi et al. (2008), Sillers et al. (2008), as well as the history of butanol production by fermentation, Villadsen (2007). Older literature references are given in Chap. 5.
You will notice that the pathway to butanol, acetone, and butyric acid is an extension of the fermentation pathways in Fig. 2.5a, b, starting with dimerization of AcCoA.
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1.
Write the pathways which lead to the products in the “solvents fermentation process.”
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What are the key issues in the process?
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How can the formation of butyric acid be (almost) suppressed, and what is the maximum yield of butanol on glucose obtained according to the references?
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4.
Find the bulk prices of 1-butanol and of technically pure glucose syrup obtained by liquefaction of starch. What is the added value of converting glucose syrup to butanol when the reported yields are used in the calculation?
Problem 2.4
Using the diagrams in a standard text on biochemistry or the much more detailed diagrams on the net you are required to write down the whole pathway from glucose to l-lysine and to l-tyrosine. This will give you an impression of the complexity of the biochemistry, but you will also notice that many parts of the total paths to the two amino acids are similar.
Problem 2.5
In Werpy and Petersen (2004), (Table 2.1), you will find diagrams that show how succinic acid can be used to produce a large number of chemicals.
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1.
Indicate the chemical processes needed to make these chemicals from succinic acid as a starting material. Could some of the chemicals also have been formed from other building blocks?
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2.
Look in recent literature for papers from the group of Sang Yup Lee at KAIST for exciting work toward production of succinic acid by fermentation. What are the issues of importance in order to get a high yield on glucose, a high productivity, and a high titer? Is the limited solution of succinic acid in aqueous solutions a problem?
Problem 2.6
In eukaryotes NAD+ is produced in the mitochondria as a result of respiration. NAD+ is needed in the cytosol (the EMP pathway). By which process is the NAD+ transferred from the mitochondria to the cytosol? The answer is found by consultation of standard textbooks on Biochemistry.
Problem 2.7
Since 2008 Cargill and Novozymes have collaborated to develop an entirely bio-based route to acrylic acid (2-propenoic acid), which is the basis for production of the hugely important acryl-based polymers. Central to their effort is to produce 3-hydroxy propionic acid (see Fig. 2.1b), which by dehydration of the alcohol gives acrylic acid.
Based on two major publications, Straathof et al. (2005) and Henry et al. (2010), you are required to review the research that within less than a decade has led to identification of the best metabolic routes to 3-hydroxy propionic acid, one of the projected platform chemicals in Werpy and Petersen(2004).
A thorough study of this problem will teach you how front-line biotech companies use all the suggestions discussed in Sect. 2.4.3 for strain development, and of pathway engineering in particular.
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Villadsen, J., Nielsen, J., Lidén, G. (2011). Chemicals from Metabolic Pathways. In: Bioreaction Engineering Principles. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9688-6_2
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