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

• Published in: Biotechnology and bioengineering 2000-08, Vol.69 (4), p.429-439
• Main Authors: Davies, J. L., Baganz, F., Ison, A. P., Lye, G. J.
• Format: Article
• Language: English
• Subjects: Antibiotics; Biological and medical sciences; Biomass; Biotechnology; Culture Media; erythromycin; Erythromycin - biosynthesis; Fermentation; fermentation medium; Fermenters; Fundamental and applied biological sciences. Psychology; Growth kinetics; Health. Pharmaceutical industry; Image analysis; Industrial applications and implications. Economical aspects; Microfiltration; Microorganisms; Production of active biomolecules; Saccharopolyspora - growth & development; Saccharopolyspora - metabolism; Saccharopolyspora erythraea; Ultrafiltration; Viscosity
• ISSN: 0006-3592; 1097-0290
• DOI: 10.1002/1097-0290(20000820)69:4<429::AID-BIT9>3.0.CO;2-5

Changes in fermentation media not only affect the performance of the fermentation 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 fermentor. In this work, microfiltration experiments to remove Saccharopolyspora erythraea biomass from fermentation broth and to recover erythromycin were carried out using two fundamentally different media; a soluble complex medium (SCM) and an oil‐based process medium (OBM). Small‐scale batch fermentations of 14‐L working volume were carried out in triplicate using both media. Broth samples were taken from each fermentation at regular intervals from the end of the exponential‐growth phase onwards. These were then processed using a Minitan II (acrylic), tangential crossflow‐filtration module, fitted with a single 60 cm2 Durapore hydrophilic 0.2 μm membrane, operated in concentration mode. The OBM fermentations produced higher titers of erythromycin but required longer fermentation times due to increased lag phases and slower maximum‐growth rates. The OBM also increased the loading on the membrane; at maximum product titers residual oil concentrations 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 found that both the permeate flux and erythromycin transmission were affected by the choice of medium. The OBM 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% respectively) when the fermentations were harvested at maximum erythromycin titers. Transmission of erythromycin stayed approximately constant as a function of fermentation time for both media, however, for the OBM the permeate flux decreased with time which correlated with an increase in broth viscosity. The relatively poor microfiltration performance of the OBM medium was, however, 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. Image‐analysis data suggested that there was a correlation between hyphal morphology (main hyphal length) and permeate flux (no such correlation was found for the OBM broth). Moreover, it has been shown for the OBM broth that the residual flour had a profound effect on the microfiltration characteristics. The influ