E. Lyagin

Continuous screening system for inhibited enzyme catalysis: A membrane reactor approach

The screening of catalysts, substrates or conditions in the early stages of bioprocess development requires an enormous number of experiments and is a tedious, expensive and time-consuming task. Currently available screening systems can only be operated in batch or fed-batch mode, which can lead to severe misinterpretations of screening results. For example, catalysts that are inhibited by substrates or accumulating products will be excluded from further investigations in the early stages of process development despite the fact that they might be superior to other candidates in a different operational mode. Important and advantageous properties such as turnover stability can also be overshadowed by product inhibition. The aim of this study was to develop a novel screening system that enables continuous feeding of substrates and continuous removal of products. A prototype based on the membrane reactor concept was designed and operated for a model reaction, the hydrolysis of cellulose.

Continuous Membrane-Based Screening System for Biocatalysis

The use of membrane reactors for enzymatic and co-factor regenerating reactions offers versatile advantages such as higher conversion rates and space-time-yields and is therefore often applied in industry. However, currently available screening and kinetics characterization systems are based on batch and fed-batch operated reactors and were developed for whole cell biotransformations rather than for enzymatic catalysis. Therefore, the data obtained from such systems has only limited transferability for continuous membrane reactors. The aim of this study is to evaluate and to improve a novel screening and characterization system based on the membrane reactor concept using the enzymatic hydrolysis of cellulose as a model reaction. Important aspects for the applicability of the developed system such as long-term stability and reproducibility of continuous experiments were very high. The concept used for flow control and fouling suppression allowed control of the residence time with a high degree of precision (±1% accuracy) in a long-term study (>100 h).