[Tracing the past half century of my microbial transformation studies]

In the middle of 1950's, microbial transformation technology was introduced into the field of synthetic chemistry as a new methodology. There was a sudden interest in research on the problems of producing steroid hormones by microbial transformation. At that time, the first project entitled "The Study for Microbial Transformation of Steroids", the "Tsuda Project", was established in the Institute of Applied Microbiology (IAM), University of Tokyo, in the spring 1956, in which I took part. This paper summarizes a number of results of our microbial transformation reactions not only in the synthesis of steroidal compounds, but also more broadly for other organic compounds, such as pravastatin, etc. The results are divided into five categories: 1) Microbial transformation of steroids, 2) Correlation between isolation sources of Pseudomonas spp. and their transformation activities, 3) Fermentation Production of prednisolone by Bacillus pulvifaciens SANK 71760, 4) Microbial transformation of siccanin, and 5) Development and fermentation production of pravastatin. About 30 years later, almost at the end of my microbial transformation studies, I had the opportunity to find some microbial strains having superior hydroxylation ability of ML-236BNa to pravastatin. Fortunately, Streptomyces carbophilus SANK 62585 was finally selected as a potent microbial converter with the formation of a lesser amount of by-products. With the view of industrial production of pravastatin, many studies and improvements were made to the culturing conditions to obtain productivity available commercially.