Continuous Δ¹-hydrocortisone dehydrogenation with in situ product recovery

A continuous aerated process for Δ¹-hydrocortisone dehydrogenation by polyacrylamide-hydrazide (PAAH) bead-entrapped A. simplex cells was developed. The process allows for stable conversion of 1.6 g l^-1 hydrocortisone (×5 the solubility in water), made possible by the incorporation of selected cosolvent [5% (v/v) triethyleneglycol]. A large difference in substrate and product solubilities in the cosolvent-buffer medium allowed for in situ product recovery in an aerated, fluidized-bed, immobilized-cell reactor by the controlled addition of fine product-adsorbing powder (microcrystalline cellulose). The product was recovered at the reactor outlet as a fine complex with the adsorbent. Stable continuous operation of at least 4 weeks was recorded for a prototype reactor configuration, followed by the exhibition of similar operational stability in a modified version of a commercially available 2.5-l airlift reactor. Our results demonstrate that in addition to an obvious desirable cosolvent effect on substrate solubility enhancement, it may also enable easy in situ product recovery by creating a large gap in the solubilities of the substrate and the product in the cosolvent-containing reaction medium.