Studies on the interaction of fermentation and microfiltration operations:Erythromycin recovery from Saccharopolyspora erythraea fermentation broths

Changes in fermentation media not only affect the performance of the fermen tation itself (with regard to the kinetics of biomass and product formation and the yields obtained) but also the initial product-recovery operations downstream of the fermenter. In this work, microfiltration experiments to r emove Saccharopolyspora erythraea biomass from fermentation broth and to re cover erythromycin were carried out using two fundamentally different media ; a soluble complex medium (SCM) and an oil-based process medium (OBM). Sma ll-scale batch fermentations of 14-L working volume were carried out in tri plicate using both media. Broth samples were taken from each fermentation a t regular intervals from the end of the exponential-growth phase onwards. T hese were then processed using a Minitan II (acrylic), tangential crossflow -filtration module, fitted with a single 60 cm(2) Durapore hydrophilic 0.2 mu m membrane, operated in concentration mode. The OEM fermentations produc ed higher titers of erythromycin but required longer fermentation times due to increased lag phases and slower maximum-growth rates. The OEM also incr eased the loading on the membrane; at maximum product titers residual oil c oncentrations of 3 g . L-1, antifoam concentrations of 2 g . L-1 and flour concentrations estimated at approximately 10 g/L-1 were typical. It was fou nd that both the permeate flux a nd erythromycin transmission were affected by the choice of medium. The OEM had significantly lower values for both parameters (12.8 Lm(-2) h(- 1) and 89.6% respectively) than the SCM (35.9 Lm(-2) h(-1) and 96.7% respec tively) when the fermentations were harvested at maximum erythromycin titer s. Transmission of erythromycin stayed approximately constant as a function of fermentation time for both media, however, for the OEM the permeate flu x decreased with time which correlated with an increase in broth viscosity. The relatively poor microfiltration performance of the OEM medium was, how ever, offset by the higher titers of erythromycin that were achieved during the fermentation. The filtration characteristics of the SCM broth did not show any correlation with either broth viscosity or fermentation time. imag e-analysis data suggested that there was a correlation between hyphal morph ology (main hyphal length) and permeate flux (no such correlation was found for the OEM broth). Moreover, it has been shown for the OEM broth that the residual flour had a profound effect on the microfiltration characteristic s. The influence of the residual flour was greater than that imposed by the morphology and concentration of the biomass. The understanding of the fact ors governing the interaction of the fermentation and microfiltration opera tions obtained in this work provides a first step towards optimization of t he overall process sequence. (C) 2000 John Wiley & Sons, Inc.