Engineering enzymes

Could we design and construct enzymes to catalyse any desired reaction? Compared with organic chemical catalysts, enzymes are highly specific and work in dilute aqueous solutions at ambient temperatures. Substrates are brought together from solution to precise orientations in the active site of an enzyme and the amino acid side-chains of the enzyme may assist catalysis by attacking or destabilizing substrate bonds. In principle, a novel enzyme could be constructed de novo or from pre-existing enzymes. Altering enzymes by recombinant DNA techniques offers most chance of success.     

Alkylating enzymes

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Highlights► Alkylating enzymes allow regiospecific and chemospecific reactions where classical chemical syntheses fail or require an extensive protection strategy. ► Prenyltransferase and methyltransferase are increasingly applicable in biotechnology. ► Cofactor or cosubstrate availability can still be a limiting factor. ► Enzyme cascade reactions and/or whole-cell systems are applied to perform multiple step transformations. ► Alkyltransferases are crucial elements in pathway engineering and synthetic biology, especially toward plant derived (natural) products.     

DNA enzymes

The past year has seen a coming-of-age in DNA enzyme research. Far from being laboratory curiosities, the activities of new DNA enzymes have broadened the known catalytic repertoire of nucleic acid enzymes, provided valuable insights into different mechanistic possiblities open to nucleic acid catalysts, and explored the importance for catalysis of native functionalities within DNA and RNA, as well as of a diversity of extrinsic cofactors. Thus, the first amino acid cofactor-utilizing DNA enzyme has been described, as well as DNA enzymes that cleave RNA without the assistance of any external cofactor. On the practical side, the most efficient RNA-cleaving nucleic acid enzyme described to date is a DNA enzyme.     

Viral enzymes

Viral genomes show unequalled diversity, ranging from single-stranded DNA to double-stranded RNA. Moreover, viruses can quickly adapt to the host's immune response and drug treatment. Although they tend to make optimal use of the host cell's reservoir of proteins, viruses need to carry some enzymatic functions with them, as they may not be available or accessible in the infected cell. Recently, progress has been made in our structural understanding of viral enzymes involved in all stages of the viral life cycle, which includes entry, hijack, replication and exit stages.