Bioprocess Technology- Fundamentals and Applications Chapt 4_Metabolic basis

Reprint from: Enfors-Häggström, Bioprocess technology- Fundamentals and Applications,KTH, Stockholm, 2000

Chapter 4. METABOLIC BASIS OF PRODUCT FORMATION

The cellular metabolism is made up of a large number of reactions co-ordinated by enzymessubjected to various control mechanisms. Some of these reactions may lead to a desiredproduct. Knowledge of metabolism and physiology constitutes the basis for developingcontrol strategies in biotechnical processes. This chapter provides a framework of metabolicand physiological features relevant to microbial processes. Textbooks on biochemistry andmicrobial metabolism should be consulted for further details. Metabolism of cultured animalcells will be treated separately (chapter 17).4.1 Metabolic organisation

A simplified overview of the primary metabolism is shown in Fig. 4.1. Metabolism can bevisualised as composed of three compartments as indicated by the boxes for catabolism,anabolism and synthesis of macromolecules

.

Fig. 4.1. Primary metabolism - an overview.

The catabolic and anabolic compartments contain biochemical pathways whereas thesynthesis of macromolecules rather is the assembly of pre-made building blocks. A flow ofmaterial runs through the three compartments, eventually resulting in the production of newcells i.e. growth. Environmental changes such as changes in substrate concentration, pH andtemperature and the accumulation of waste products follow from this process.

Glycolysis:

Respiration:

ATP

Acetyl-CoA

NAD+

H O

2

TCA-cycle:

NADH

O2

ADP

CO

2

Fig 4.2. Aerobic energy metabolism- a simplified overview. The reduced energy substrate(glucose) is oxidised to pyruvate by NAD+ in a series of reactions called glycolysis. thisgenerates a small amount of the energy carrier ATP. Pyruvate is further oxidised to CO2 byco-enzymes (NAD+) in the TCA-cycle. The reduced coenzymes (NADH) are re-oxidised (NAD+ ) in the respiratory chain, where molecular oxygen is the ultimate receiver of theelectron. This oxidation is coupled to generation of a relatively large amount of ATP.

In anaerobic respiration, nitrate, sulphate or some other oxidised specie is used as electronacceptor instead of molecular oxygen. In fermentative energy metabolism, the NADH fromthe glycolysis is reoxidised by reduction of pyruvate to fermentation products like ethanol,lactate etc. (Fig 4.6-4.7)

The entrance of substrates into the catabolic compartment is the starting point for all theseactivities. The catabolic compartment contains the central metabolic pathways i.e. glycolysis,the hexose monophosphate shunt (HMS) and the pentose cycle, the tricarboxylic acid cycle(TCA) as well as respiration and the generation of the energy carrier ATP (Fig. 4.2). (Inaddition to the aerobic heterotrophic metabolism - other types of energy metabolism likeaerobic autotrophic, anaerobic fermentation, anaerobic respiration and photosynthesis occurin microorganisms.) NAD+/NADH are, with few exceptions, recirculated within thecatabolic compartment. Intermediate metabolites from the catabolic pathways constitute theprecursors for biosynthesis of building blocks in the anabolic compartment. Catabolism alsofurnishes the reducing power (NADPH) required for biosynthesis.

Anabolism is the synthesis of building blocks used for macromolecule synthesis. Here, thewell known pathways for amino acid and nucleotide synthesis are harboured as well as thesynthesis of fatty acids and sugar moieties. Finally, these building blocks are assembled intomacromolecular constituents of the cell like DNA, RNA, protein, membrane lipids and cellwalls.

Products produced in biotechnical processes may originate from any of the three metaboliccompartments in Fig. 4.1, or constitute the result of them all as in the production of bakersyeast or clean water in a sewage plant. The characteristics of product formation in themetabolic compartments will be described later in sections 4.6, 4.7 and 4.8. However, the

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