Catabolite inhibition

Thompson, J. D., Turner, K. W. and Thomas, T. D. 1978. Catabolite inhibition and sequential metabolism of sugars by Streptococcus lactis. J. BacterioL 133, 1163-1174. 

Two other types of catabolite regulation are known. In catabolite inhibition , catabolites of a rapidly used carbon source inhibit the action of other enzymes. When an enzyme is actually inactivated by catabolites, the phenomenon is known as catabolite inactivation . Much less is known about the significance of these forms of catabolite regulation. 

Avoiding Substrate Inhibition, Enzymatic Inhibition, and Catabolite Repression When using the fed-batch operation, the concentration of a substrate can be kept at a low value so that substrate inhibition, enzymatic inhibition, or catabolite repression is practically avoided, which results in high productivity [14]. 

In addition to catabolite repression, the cellulase enzymes themselves are subject to end-product inhibition. For example, as glucose accumulates during saccharification, it interacts noncompetively with cellobiase to inhibit further activity of this enzyme (6). Similar inhibition of endoglucanases occurs when cellobiose accumulates in a saccharification reactor (18,19,20). 

Isolation of Constitutive> Catabolite Repression, and End-Product Inhibition-Resistant Mutants... 

For example, for deciding on the type of carbon source, the phenomenon of catabolite repression must be considered. Similarly, regulation of nitrogen and sometimes phosphorus metabolism are important factors to consider. Sometimes high concentrations of salts and free amino acids necessary for high cell density are inhibitory to product formation. One area often overlooked is the elimination of unwanted impurities, derived either from the raw material or produced via metabolism. These impurities represent not only a waste of the carbon source, but their accumulation at high levels may lead to inhibition of growth or even cell death. 

All the DNA-binding proteins discussed thus far function by inhibiting transcription until some environmental condition, such as the presence of lactose, is met. There are also DNA-binding proteins that stimulate transcription. One particularly well studied example is the catabolite activator protein (CAP), which is also known as the cAMP response protein (CRP). When bound to cAMP, CAP, which also is a sequence-specific DNA-binding protein, stimulates the transcription of lactose- and arabinose-catabolizing genes. Within the lac operon, CAP binds to an inverted repeat that is centered near position -61 relative to the start site for transcription (Figure 31.10). CAP functions as a dimer of identical subunits. 

Frumento G, Rotondo R, Tonetti M, Damonte G, Benatti U, Ferrara GB (2002) Tryptophan-derived catabolites are responsible for inhibition of T and natural killer cell proliferation induced by indoleamine 2, 3-dioxygenase. J Exp Med 196 459-468... 

The biosynthetic source of the pyridone ring of 87 was investigated [260]. Thymine was found to inhibit uracil catabolism and 87 biosynthesis by Nocardia lactamdurans this inhibition was reversed by uracil catabolites. Both [5,6-3H]-uracil and [4,5-13c]-uracil were incorporated, with both labelled carbons of the latter being incorporated as a unit at C(4) and C(5) of 87. The proposed biosynthetic pathway (Scheme 2) involved catabolism of uracil to p-alanine, which was then incorporated into the pyridone ring of 87 [260]. 

The red chlorophyll catabolite RCC (11) is bound strongly to PaO and inhibits it. In an in vitro assay, the soluble reductase from oilseed rape converted 11 to the primary fluorescent chlorophyll catabolite pFCC (10, 31,32-didchydro-1,4,5,10,17,18,20-(22//)-octahydro-132-(mcthoxy-carbonyl)-4,5-dioxo-4,5-seco-phytoporphyrin) (62, 83). The reductase, which was named red chlorophyll catabolite reductase (RCC-reductase) (68, 80, 83), introduced the chiral center C(l) via a stereo-selective reduction step. However, early studies with oilseed rape and sweet pepper indicated a remarkable stereo-dichotomy of the respective reductases (see above) (67, 68, 69). Screening of a variety of plant species for their type of primary FCC revealed the broad existence of two classes of the RCC-reductases , whose stereo-selectivity was species specific (84). At present, the (absolute or relative) configuration at C(l) in the two pFCCs (10 and epi-10) is not yet established (2). Indeed, the existence of the two epimeric pFCCs (10 and epi-10) (see Scheme 6) indicated the absolute configuration at the newly generated chiral center to have no apparent functional relevance (67, 68, 69). 

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