Premium
Application of computer to monitoring and control of fermentation process: Microbial conversion of ML‐236B Na to pravastatin
Author(s) -
Hosobuchi Masahiko,
Kurosawa Kazuyuki,
Yoshikawa Hiroji
Publication year - 1993
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.260420705
Subject(s) - fermentation , hydroxylation , pravastatin , chemistry , chromatography , industrial fermentation , biochemistry , reductase , enzyme , cholesterol
An automatic feeding process for microbial hydroxylation of ML236B sodium salt (ML‐236B Na; compactin) by Streptomyces carbophilus SANK 62585 was developed. The hydroxylated product, pravastatin sodium salt (pravastatin; trade name Mevalotin), is an inhibitor of 3‐hydroxy‐3‐methyglutaryl–coenzyme A reductase (HMG–CoA reductase) used as cholesterol‐lowering drug. The hydroxylation activity of S. carbophilus was induced by the addition of ML236B Na to culture broth but inhibited by high concentration of ML236B Na. In order to obtain high conversion yield, it was necessary to maintain optimum ML236B Na concentration throughout the fermentation by continuous feeding. For this purpose, we developed an on‐line monitoring method, which mainly consisted of a cross‐flow filtration module, high‐performance liquid chromatography (HPLC) analyzer, feed pump, and microcomputer for regulation of ML236B Na concentration. An algorithm for control of ML236B Na feed rate based on feedback and feed‐forward control where conversion rate after Δ t was estimated by using regression analysis of the five latest values of conversion rate. In a fed‐batch culture employing this system, the concentration of ML236B Na was maintained at optimum level during the fermentation and the productivity of pravastatin was increased threefold over that obtained in manual control culture. © 1993 John Wiley & Sons, Inc.