Protein Engineering for the Production of Specific Chemicals

The ability of aromatic hydrocarbon dioxygenases to catalyze reactions with a wide range of substrates has made them particularly useful for tire production of complex chiral chemicals that would otherwise be difficult, expensive, and enviroiunentally 

Examples of biologically active compoxmds produced through whole-cell oxidative reactions at an industrial scale were reviewed by Munoz-Solano et al. [56] and Matsui et al [13]. A few are described in detail here and addihonal examples are shown in Table 17.2. 

Recombinant E. coli expressing the nitrobenzene dioxygenase from Cotncmonas sp. JS765 with amino acid substitutions at position 258 or 293 was used to increase the production of chiral sulfoxides from thioanisole, p-tolyl, Cl-thioanisole, and Br-thioanisole [44]. Chiral sulfoxides are mostly known as important precursors in the pharmaceuhcal industry [13]. For example, modafinil, marketed imder the name Provigil by Cephalon and prescribed for the treatment of imcontrollable sleepiness caused by narcolepsy or sleep apnea, has a chiral sulfoxide center [57, 58]. Esomeprazole, another chiral sulfoxide, is marketed by AstraZeneca imder the name Nexium as a proton pump inhibitor that reduces gastric acid secretion for treatment of gastroesophageal reflux disease [59]. 

Enzyme Organism Substrate ds-Dihydrodiol intermediate Potential End Product Reference 

Toluene dioxygenase Pseudomonas putida UV4 Toluene Toluene 2,3-ds-dihydrodiol 6C-Methyl-D-mannose [50] 

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