CHAPTER 12

BIOCHEMICAL REACTION ENGINEERING

Biochemical engineering is a vibrant branch of chemical engineering with a signicant current presence and even greater promise for the future. In terms of development, it can be compared with the petrochemical industry in the 1920 s. Despite its major potential, biochemical engineering has not yet been integrated into the standard undergraduate curriculum for chemical engineers. This means that most graduates lack an adequate background in biochemistry and molecular biology. This brief chapter will not remedy the deciency. Instead, it introduces those aspects of biochemical reactor design that can be understood without detailed knowledge of the underlying science. A chemical engineer can make contributions to the eld without becoming a biochemist or molecular biologist, just as chemical engineers with sometimes only rudimentary knowledge of organic chemistry made contributions to the petrochemical industry. Proteins are key ingredients to life and to biochemistry. They are linear polymers of amino acids. The general formula for an amino acid is COOH H2 NC H R where R represents one of twenty dierent radicals found in nature. The amino and carboxy groups condense and eliminate water to form proteins. When proteins are formed by a living cell, the sequence of amino acids is dictated by the DNA within the cell. The term genetic engineering refers to manipulation of DNA to alter the recipe. Despite the name, genetic engineering is not an engineering discipline, but is a branch of molecular biology similar in spirit to organic synthesis. This chapter is not concerned with genetic engineering as such. Biochemical engineering (or sometimes agricultural engineering) comes later when genetically engineered organisms are to be grown in mass. Many current applications of biochemical engineering are based on naturally occurring
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CHEMICAL REACTOR DESIGN, OPTIMIZATION, AND SCALEUP

organisms and biocatalysts. The products range from small, simple molecules such as methane and ethanol, to moderately complex compounds such as penicillin, to therapeutic proteins such as human growth factor, to whole cells such as yeast, and potentially to multicell aggregates such as skin. Some of these compoundse.g., ethanol and penicillincan be produced by traditional organic synthesis. Thus, a working distinction between biochemical reaction engineering and ordinary reaction engineering is the involvement of biocatalysts, specically proteins having catalytic activity and known as enzymes.

12.1

ENZYME CATALYSIS

Enzymes are proteins that catalyze reactions. Thousands of enzymes have been classied and there is no clear limit as to the number that exists in nature or that can be created articially. Enzymes have one or more catalytic sites that are similar in principle to the active sites on a solid catalyst that are discussed in Chapter 10, but there are major dierences in the nature of the sites and in the nature of the reactions they catalyze. Mass transport to the active site of an enzyme is usually done in the liquid phase. Reaction rates in moles per volume per time are several orders of magnitude lower than rates typical of solid-catalyzed gas reactions. Optimal temperatures for enzymatic reactions span the range typical of living organisms, from about 4 C for cold-water sh, to about 40 C for birds and mammals, to over 100 C for thermophilic bacteria. Enzymatic reactions require very specic molecular orientations before they can proceed. As compensation for the lower reaction rates, enzymatic reactions are highly selective. They often require specic stereoisomers as the reactant (termed the substrate in the jargon of biochemistry) and can generate stereospecic products. Enzymes are subject to inhibition and deactivation like other forms of catalysis. 12.1.1 Michaelis-Menten and Similar Kinetics Suppose the reaction S ! P occurs using an enzyme as a catalyst. The following reaction mechanism is postulated: S E ! SE SE P E ! SE K sE R kSE

where s denotes the substrate concentration, E denotes the active site, and SE denotes the adsorbed complex. This mechanism is somewhat dierent than that used for gassolid catalysis since there is no explicit desorption step. In essence, product desorption is assumed to be instantaneous. The site balance is [SE] [E] E0

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Substituting for [SE] and [E] gives R R E0 k ksK and R E0 ks k0 s 1=K s 1 kS s 12:1

which is the functional form expected when there is competition for active sites. Just as for gassolid reactions, the reaction rate for a rst-order reaction depends linearly on the amount of catalyst and hyperbolically on the reactant concentration. See Figure 12.1(a). Biochemists usually express Equation (12.1) as R E0 ks R max s KM s KM s 12:2

4 (=)
Substrate concentration = (a)

4 (=)
Substrate concentration = (b)

4 (=)
Substrate concentration = (c)
FIGURE 12.1 Eects of substrate (reactant) concentration on the rate of enzymatic reactions: (a) simple Michaelis-Menten kinetics; (b) substrate inhibition; (c) substrate activation.