Unrelated substrate

TCE is not able to support the growth of a single organism, but it is susceptible to cooxidation by oxygenases elaborated by organisms dnring growth with structurally unrelated substrates. A review of methanotrophic bacteria (Hanson and Hanson 1996) contains a useful account of their application to bioremediation of TCE-contaminated sites. 

Induction of catabolic enzymes by growth with structurally unrelated substrates... 

There is considerable interest in synthesizing copolymers. This is actually possible if organisms are confronted with mixtures of so-called related and unrelated substrates. Copolymers can also be synthesized from unrelated substrates, e.g., from glucose and gluconate. The 3-hydroxydecanoate involved in the polyester is formed by diversion of intermediates from de novo fatty-acid synthesis [41,42]. Related , in this context, refers to substrates for which the monomer in the polymer is always of equal carbon chain length to that of the substrate offered. Starting from related substrates, the synthesis pathway is closely connected to the fatty-acid /1-oxidation cycle [43]. In Pseudomonas oleovor-ans, for example, cultivated on octane, octanol, or octanoic acid, the synthesized medium chain length polyester consists of a major fraction of 3-hydroxyoc-tanoic acid and a minor fraction of 3-hydroxyhexanoic acid. If P. oleovorans is cultivated on nonane, nonanol, or nonanoic acid, the accumulated polyester comprises mainly of 3-hydroxynonanoate [44]. 

CYP is a family of different enzymes. Each variation has a slightly different function, but all are able to accept substrates with a range of structure. Their active sites tend to be broad and shallow so that almost any compound can tit to some degree. Table 4.3 shows the variety of reactions that can be performed by CYP3A4, a common form of CYP.21 Despite unrelated substrate structures, the Km values (binding affinities) are fairly uniform. A more thorough treatment of drug metabolism will be presented in Chapter 8. 

A4 Midazolam, Testosterone (strongly recommended to use at least two structurally unrelated substrates) Nifedipine, Felodipine, Cyclosporine, Terfenadine, Erythromycin, Simvastatin Ketoconazole (recent evidence that it is also a potent inhibitor of 2C8), Troleandomycin Cyclosporine... 

As one may expect from the electron transfer reactions catalyzed by peroxidases, the rates of Col and Coll reduction by a substrate series with different substituents correlated well with the oxidizability (i.e., the E value) of the substrates [33], However, in the case of structurally unrelated substrates, this is not the only factor to be taken in to account in determining the oxidation rate, since a certain degree of substrate specificity, controlled by the enzyme and the reorganization energies of electron transfer within the enzyme-substrate transition species complex, appears to be the determining factor [33],... 

Mycobacteria can oxidize short-chain alkenes (DeBont et al. 1980), and organisms known under the invalid specific name Mycobacterium paraffini-cum (Wayne et al. 1991) are able to degrade a number of alkanes. It has also been shown that strains of mycobacteria grown with propane are able to oxidize the apparently unrelated substrate trichloroethylene (Wackett et al. 1989). There has also been a revival of interest in the role of mycobacteria in the degradation of aromatic polycyclic hydrocarbons including naphthalene (Kelley et al. 1990), phenanthrene (Guerin and Jones 1988), and pyrene... 

Although toluene degradation in pseudomonads may be induced by growth with the substrate or closely related aromatic compounds, it may also be induced by exposure to apparently unrelated substrates (1) by trichloro-ethene in a strain of P. putida (Heald and Jenkins 1994) and (2) in P. mendocina strain KR1 by trichloroethene, pentane, and hexane, although not in Burkholderia (Pseudomonas) cepacia, or P putida strain FI (McClay et al. 1995). 

Among all ABC transporters, P-gp, also known as MDRl protein, ABCBl or CD243, is probably the most studied and characterized member. It was first found as a 170-kDa ATP-dependent membrane glycoprotein that acts as a drug efflux pump [15], P-gp is a broad-spectrum transporter, capable of transporting several structurally and functionally unrelated substrate molecules. Its substrates are typically hydrophobic, amphipathic products, including many chemotherapeutic compounds used for cancer treatment, e.g., vinca alkaloids (vincristine, vinblastine), taxanes (paclitaxel, docetaxel), epipodophyllotoxins (etoposide, teniposide), anthracyclines (doxorubicin, daunorubicin, epirubicin), topotecan, dactinomycin, and mitomycin-C [37]. 

Similar metallacycles have also been prepared from unrelated substrates (a) Reaction of y,8-unsaturated sulfinilic acids with platinum(O) complexes Hallock, J. S. Galiano-Roth, A. S. Collum, D. B. Organometallics 1988, 7, 2486 (b) Reaction of y,8-unsaturated carboxylic acids with rhodium(I) complexes Marder, T. B. Chan, D. M.-T Fultz, W. C. Milstein, D. J. Chem. Soc., Chem. Commun. 1988,996 (c) Activation of a, P, y, 8, or e C-H bonds with platinum(II) complexes Kao, L.-C. Sen, A. J. Chem. Soc., Chem. Commun. 1991,1242. 

The following observations argue in favor of peptide intermediates. In enzyme adaptations of yeast cells carried out in the absence of an external supply of nitrogen there is a loss of one or more of the enzymes pre-existing in the cells. Yeast cells incubated in the presence of two metaboli-cally unrelated substrates do not normally adapt simultaneously either substrate alone does induce adaptation of the homologous enzyme. In E. coli there appears to be a relation between adaptively formed lactase and an enzymatically inactive but antigenically related protein which decreases during adaptation. 

Rodrigues M F A, da Silva L F, Gomez J G C, Valentin H E and Steinbuchel A (1995) Biosynthesis of poly(3-hydroxybutyric add-co-3-hydroxy-4-pentenoic acid) from unrelated substrates by Burkholderia sp, Appl Microbiol Biotech 43 880-886. 

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