April 15, 2009 (Vol. 29, No. 8)
A division of Richmond Chemical, Ingenza uses its biocatalytic processes and engineered enzymes to produce single-isomer chiral intermediates such as unnatural amino acids and chiral amines. The company first adapts the enzyme toward the target molecule using solid-phase screening methods. The enzymes are overproduced in microbes and optimized for production of active protein by high cell density fermentation. The organisms are used in the bioprocess either as a concentrated slurry, or minimally fractionated or dried preparations from which cellular debris has been removed.
Currently, the biocatalysts are prepared at facilities close to where the chemical synthesis takes place, and used as soon as possible after isolation. Ingenza, however, is now scaling-up drying procedures to facilitate enzyme storage and shipping for flexible large-scale manufacture.
“Ideally we take the biocatalyst preparation out of the fermentor, and use it directly in the biotransformation,” says Ian Fotheringham, Ph.D., director of biosciences. “We might, in some cases, lyse the cells and minimally fractionate the extract by centrifugation to remove cell debris such as membranes and nucleic acids.”
Not needing to prepare enzymes to high purity spares considerable downstream resources for Ingenza, but the real savings occur in the application of biocatalysts.
Aqueous enzymatic reactions are inherently cleaner than those run in organic solvents, so solvent recovery is greatly reduced or eliminated. Enzymes are infinitely more selective than most chemical reagents as well, so removing side products is not as common as it would often be for organic reactions. Many products simply crystallize out. Finally, enzymes don’t waste half of a prochiral reagent, thereby saving on starting materials and eliminating chiral resolution steps.