Specificity novel substrate specificities

Evolutionary Generation of Enzymes with Novel Substrate Specificities... 

This chapter focuses on the creation of novel substrate specificities of enzymes. Although in principle, this would also include altered enantio- or stereoselectivity, this aspect is already covered extensively in Chapter 11. 

With this in mind, it is not surprising that the examples reported in the literature (Table 14.1) for novel substrate specificities by directed evolution can be subdivided into the following three groups (Scheme 14.1) ... 

Tab. 14.1. Examples for the evolutionary generation of enzymes with novel substrate specificities.

Scheme 14.2. Structures of compounds used (la,b, 4) and obtained (2,3) by directed evolution of biocatalysts aiming at novel substrate specificities.

J. Liu, N. W. Shworak, P. Sinay, J. J. Schwartz, L. Zhang, L. M. Fritze, R. D. Rosenberg, Expression of heparan sulfate D-glucosaminyl 3-O-sulfotransferase isoforms reveals novel substrate specificities. J. Biol. Chem. 1999 274, 5185 92. 

Characterization of Substrate-specificity for Cutinase Produced by Novel Pseudozyma aphidis Isolated from Pea Leaves in South Korea... 

As each BVMO is limited in substrate specificity, it is crucial to have a large collection of these oxidative biocatalysts available. Except for expanding the scope of possible reactions, a large toolbox of BVMOs would also increase the chance of being able to perform any wanted specific chemo-, regio- and/or enantioselective reaction. This contrasts with the present situation as only a relatively small number of BVMOs can be exploited for biocatalytic purposes. Therefore, it is still crucial to discover or engineer BVMOs with novel biocatalytic properties. 

Bevers LE, E Bol, P-L Hagedoorn, WR Hagen (2005) WOR5, a novel tungsten-containing aldehyde oxidoreductase from Pyrococcus furiosus with a broad substrate specificity. J Bacteriol 187 7056-7071. 

In Fig. 5, the biosynthetic pathways for the production of PHA with novel composition of hydroxyalkanoates and the enzymes involved are shown. The level of metabolic intermediates, which is determined by the cellular metabolic activities, is important for the synthesis of a desired PHA. Having the engineered metabolic pathways at hand, PHA synthase plays an important role affecting the composition of PHAs, because of substrate specificity of PHA synthase. 

The study of DUBs has moved at a rapid rate since their initial discovery in the early 1980s. Yet despite all the progress, the total number of DUBs and the substrate specificity of most DUBs are still undetermined. The discovery of novel DUB families including the JAMM isopeptidases and OTU DUBs has highlighted that there may be still more unidentified DUBs. Because of the large number of... 

Kim, I., Song, X., Vig, B.S., Mittal, S., Shin, H.-C., Lorenzi, P.J. and Amidon, G.L., A novel nucleoside prodrug-activating enzyme substrate specificity of biphenyl hydrolase-like protein. Mol. Pharm., 2004,1, 117-127. 

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