Abstract

Complex raw materials are widely used as supplements in biopharmaceutical production processes due to their positive effect on biomass growth and productivity at low cost. However, their use negatively impacts process reproducibility due to high lot-to-lot variability which contradicts current regulatory guidelines. In this study we investigated crude soy bean oil (SBO) which is a common complex raw material for filamentous fungi. We demonstrated that lecithin, which we define as phosphatidylcholines, is in fact the key material attribute in crude SBO positively affecting fungal growth and consequently productivity. The methodological toolbox we present here allows the straightforward isolation of lecithin from crude SBO, its semi-quantification by HPLC and the consequent supplementation thereof in defined amounts. Thus, over-dosage and potential resulting negative impacts on fungal growth and productivity can be omitted.

Highlights

  • Complex raw materials are commonly used as cheap media supplements in bacterial, fungal and mammalian bioprocesses (Gao and Yuan 2011; Millis et al 1963; Reese and Maguire 1969)

  • soy bean oil (SBO) as typical complex raw material Typical characteristics of complex raw materials are their positive impact on growth and productivity at low cost, and their negative impact on process reproducibility due to high lot-to-lot variability

  • In the main culture phase the supplementation with crude SBO led to an increase in product concentration up to almost 50%

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Summary

Introduction

Complex raw materials are commonly used as cheap media supplements in bacterial, fungal and mammalian bioprocesses (Gao and Yuan 2011; Millis et al 1963; Reese and Maguire 1969). These raw materials are typically of biological origin and underlie a high lot-to-lot variability. Material attributes do affect product quality and process performance and productivity. We define these material attributes that have an impact on productivity as key material attributes (kMAs). Identification of CMAs and kMAs, sound science-based knowledge of raw material quality has become a necessity

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