A Three-Enzyme Process for Atorvastatin Intermediate

A two-step three-enzyme process for atorvastatin intermediate. 

Similarly, the activity of the wild-type HHDH in the nonnatural cyanation reaction was extremely low, and the enzyme exhibited severe product inhibition and poor stability xmder operating conditions. However, after many iterative roxmds of DNA shuffling, the inhibition was largely overcome and the HHDH activity was increased more than 2500-fold compared to the wild-type enz5une. 

The greenness of process was assessed according to the 12 principles of green chemistry  

Principle 2—AE The use of glucose as the reductant for cofactor regeneration is cost-effective, but the AE is poor (45%). However, glucose is an inexpensive renewable raw material and the gluconate coproduct is fully biodegradable. 

Principle 3—less hamrdcms chemical syntheses The reduction reaction uses essentially nontoxic starting materials and avoids the use of potentially hazardous hydrogen and heavy metal catalysts obviating concern for their removal from waste streams and/or contaminahon of the product. While cyanide must be used in the second step, as in all practical routes to the product, it is used more efficiently (higher yield) and under less harsh conditions compared to previous processes. 

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