The effects of fermentation conditions on yeast cell debris particle size distribution during high pressure homogenisation

Siddiqi, S. F.; Bulmer, M.; Shamlou, P. Ayazi; Titchener-Hooker, NJ

doi:10.1007/bf00369846

Cited by 25 publications

(27 citation statements)

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“…6). A single peak is typically seen for packed bakers' yeast [23] although bi-modal distributions were observed by Siddiqi et al [24] for some batch fermented samples of bakers' yeast. Microscopic examination and counting of the S. cerevisiae strain MC1 whole cells indicated that the larger peak was mostly composed of budded cells, while the smaller peak contained single cells.…”

Section: Debris Psd Modellingmentioning

confidence: 98%

“…Siddiqi et al [23,24] have developed an empirical model describing the change in debris PSD characteristics under various homogeniser processing conditions for packed bakers' yeast and fermented bakers' yeast at different stages of growth. Whole cell and resultant debris PSDs are described by Boltzman equations:…”

Section: Modelling Of Yeast Homogenisationmentioning

confidence: 99%

“…For packed bakers' yeast P t equals 115 barg and k has a value of 670 pass A0.4 barg A1 . In the case of fermented yeast the value of k was found to be strongly dependent on the culture conditions and ranged from 670 to 2200 pass A0.4 barg A1 over a 30 hour batch fermentation and from 700 to 1370 pass A0.4 barg A1 for continuous fermentation at dilution rates between 0.06 and 0.26 h A1 [24].…”

Section: Modelling Of Yeast Homogenisationmentioning

confidence: 99%

“…Equations (6) to (10) were used as the basis for determining debris PSDs, with a k value of 1100 pass A0.4 barg A1 used in Eq. (7) as this corresponded to cellular properties at the fermentation time used for the recombinant strain [24]. In assessing model results, a level of accuracy of 30% was regarded as suf®cient for feasibility and initial design studies [4], while greater accuracy, of the order 10% and less, was required for detailed design calculations and the determination of optimal process operating conditions.…”

Section: Modelling Of Yeast Homogenisationmentioning

confidence: 99%

“…(6), were ®tted to the experimental PSD's enabling values of d 50 and x to be determined and compared to values predicted by the PSD model, Eqs. (7) to (10), using batch fermented bakers' yeast model parameters [24]. It should be noted that the S. cerevisiae MC1 strain whole cell PSD contained two distinct peaks i.e.…”

Section: Debris Psd Modellingmentioning

confidence: 99%

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Use of scale-down methods to rapidly apply natural yeast homogenisation models to a recombinant strain

Varga

Titchener-Hooker

Dunnill

1998

Bioprocess Engineering

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Models for high pressure homogenisation developed using natural bakers' yeast were applied to a recombinant yeast strain. The models were found to be generic in nature and generally adequate for initial process design (30%). More accurate descriptions (10%) of the release of protein engineered enzyme product, the release of total soluble protein and the change in debris size distribution required a small amount of extra information which was readily acquired using a scale-down unit. Utilisation of such scale-down and modelling techniques will enable design calculations, unit integration and identi®-cation of optimum operating conditions to be carried out for the high pressure homogenisation of recombinant yeast early in process development with a high degree of con®dence.List of symbols b constant in Eq. (5) C u soluble protein assay result (mg/ml) C y yeast concentration on a wet weight basis (g/l) d particle diameter (lm) d 50 Boltzman average diameter (lm) d 50N0 whole cell Boltzman average diameter (lm) d Ã 50 dimensionless form of d 50 de®ned as d 50N0 À d 50 ad 50N0 À D fraction of cells disrupted À F aqueous fraction À f D S stress distribution imposed on cells by homogeniser À f S S cell strength distribution À f d NYP cumulative (undersize) volume PSD for a given size range at given P and N i number of data points À k constant in Eq. (7) K constant in Eq. (1) m constant in Eq. (5) n constant in Eq. (5) N number of passes À Q¯owrate (m/s 3 ) P pressure (barg) P t threshold pressure (barg) r regression coef®cient À R soluble protein release (mg protein/ g wet weight yeast) R max maximum soluble protein release (mg protein/g wet weight yeast) S effective strength À S m mean effective strength À Greek symbols a exponent in Eq. (1) r standard deviation À x Boltzman parameter in Eq. (6) x N0 whole cell Boltzman parameter in Eq. (6) x Ã dimensionless form of x de®ned as (x N0 À xx N0 À v chi statistic R centrifuge sigma factor (m 2 ) IntroductionThe use of the yeast Saccharomyces cerevisiae as a host organism for the production of recombinant proteins often results in an intracellular product [9]. Ef®cient cell disruption is therefore required to achieve product release and enable subsequent recovery. High pressure homogenisation is usually the preferred unit operation for achieving this disruption at a large scale [20]. In determining process feasibility and for subsequent engineering design it is essential that the homogenisation stage can be described by relevant mathematical models. With increasing pressure on biotechnology companies to bring bioproducts to market in the shortest possible time and at low cost, there is also a need to produce unit and process models early in the process development cycle from only small amounts of sample material and with a minimum of effort. This provides the incentive for scaledown research in which accurate mimics of key unit operations are developed which require only limited quantities of feed material but can generate useful process information [13].

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Section: Debris Psd Modellingmentioning

confidence: 98%

Section: Modelling Of Yeast Homogenisationmentioning

confidence: 99%

Section: Modelling Of Yeast Homogenisationmentioning

confidence: 99%

Section: Modelling Of Yeast Homogenisationmentioning

confidence: 99%

Section: Debris Psd Modellingmentioning

confidence: 99%

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