Development of a pilot‐scale microfiltration harvest for the isolation of physostigmine from Streptomyces griseofuscus broth

Abstract

AbstractA pilot‐scale microfiltration harvest was developed for the isolation of physostigmine from a mycelial fermentation broth. Complete permeation for this extracellular secondary metabolite was obtained during initial laboratory screening with a variety of crossflow filtration membranes but poor filtration flux made process feasibility uncertain. Modification of the fermentation medium improved fluxes from 10–20 dm3 m−2 h−1 to 60–80 dm3 m−2 h−1 which significantly reduced membrane area requirements, making the process feasible for larger scale implementation. A commercially‐available ceramic membrane with 0·2 μm pores was employed for the scale‐up of this step to the pilot plant; this membrane was found to provide flux similar to that of polymeric membranes and had superior regeneration characteristics. Optimum performance at bench scale was obtained using 70 kPa transmembrane pressure and 4·0 m s−1 crossflow velocity. The mycelial broth had a very high suspended solids concentration (30% (v/v)) which limited us to a two‐fold concentration before starting the diafiltration washes. The process was scaled‐up to the 200–400 dm3 scale, with good reproducibility and excellent membrane regenerability observed in a series of five experiments. An increase in membrane loading did result in a decreased average flux at the larger scale (47·6 dm3 m−2 h−1), which indicated the importance of this parameter. A centrifugal pump was substituted for a positive displacement pump upon scale‐up and performed well if provided with the appropriate suction head. Scale‐up in general was straightforward, provided proper attention was given to the hydraulic design of the system.