Physiological description of multivariate interdependencies between process parameters, morphology and physiology during fed‐batch penicillin production

Abstract

Optimization of productivity and economics of industrial bioprocesses requires characterization of interdependencies between process parameters and process performance. In the case of penicillin production, as in other processes, process performance is often closely interlinked with the physiology and morphology of the organism used for production. This study presents a systematic approach to efficiently characterize the physiological effects of multivariate interdependencies between bioprocess design parameters (spore inoculum concentration, pO2 control level and substrate feed rate), morphology, and physiology. Method development and application was performed using the industrial model process of penicillin production. Applying traditional, statistical bioprocess analysis, multivariate correlations of raw bioprocess design parameters (high spore inoculum concentration, low pO2 control as well as reduced glucose feeding) and pellet morphology were identified. A major drawback of raw design parameter correlation models; however, is the lack of transferability across different process scales and regimes. In this context, morphological and physiological bioprocess modeling based on scalable physiological parameters is introduced. In this study, raw parameter effects on pellet morphology were efficiently summarized by the physiological parameter of the biomass yield per substrate. Finally, for the first time to our knowledge, the specific growth rate per spore was described as time-independent determinant for switching from pellet to disperse growth during penicillin production and thus introduced as a novel, scalable key process parameter for pellet morphology and process performance.

Salt‐enhanced cultivation as a morphology engineering tool for filamentous actinomycetes: Increased production of labyrinthopeptin A1 in Actinomadura namibiensis

“…A transition from pellet to dispersed morphology, i.e., the disintegration from pellets into looser fragments after a certain period of cultivation time, was also reported for bioreactor cultivations of Penicillium chrysogenum under diverse process conditions . Posch and Herwig found that this effect depends on the specific growth rate normalized with respect to the spore inoculum concentration used and, to a lesser degree, on the fraction of the culture of P. chrysogenum present in pellet morphology.…”

Optimal process design space to ensure maximum viability and productivity in Penicillium chrysogenum pellets during fed-batch cultivations through morphological and physiological control

“…After the batch, the broth was diluted with fed-batch medium (15% broth, 85% medium) and fed-batches were started. Details on batch and fed-batch media can be found in Posch and Herwig [15].…”

The Taming of the Shrew - Controlling the Morphology of Filamentous Eukaryotic and Prokaryotic Microorganisms

“…Fungal morphology is often a bottleneck of productivity in many industrial processes [91], and process optimisation requires the accurate characterisation of interdependencies between process parameters and performance [92]; therefore, from the very beginning of research with filamentous organisms, it has always been a goal to characterise and model morphology [93][94][95]. For the quantification of filamentous morphology, early studies relied on manual measurements of hyphal growth [96,97].…”