Enantioselective whole-cell biotransformation of acetophenone to S-phenylethanol by Rhodotorula glutinis Part I. Product formation kinetics and feeding strategies in aqueous media

摘要

This work explores product-formation kinetics of the reduction of acetophenone to (S)-phenylethanol by Rhodotorula glutinis in aqueous media. Different feeding strategies were investigated to improve biotransformation productivity. An empirical kinetic model was formulated considering two different reaction periods: Phase-1, a very fast chemical-shock reaction in the first 5min; Phase-2, a subsequent slower reaction which, depending on the product level, could be subinhibitory or inhibitory. The kinetics of the biotransformation metabolism were modulated by the levels of glucose and acetic acid in the bioreactor. In addition, two substrate feeding regimes were compared: intermittent and continuous. Although similar overall productivities were found, the intermittent method clearly holds greater potential for enhanced space-time yields as it takes advantage of the Phase-1 high reaction rates - additions of substrate pulses produce reaction rates of the same order of magnitude as those achieved in Phase-1. However, product accumulation to a "toxic limit" leads to the total cessation of biocatalytic activity, thus highlighting the importance of in-situ product removal during the biotransformation. Strategies for in-situ product removal are addressed in Part II of this study.