A main objective of research on antibiotics is to find new active agents. In this research, it is most important to explore new research areas where new microbial products with potential usefulness can be found. By 1965, exten sive advancement took place in the chemistry of natural products and made possible the elucidation of the structure of low-molecular-weight com pounds in a short period of time. Moreover, the research in enzymology of biological functions and disease processes began to show rapid progress. It seems logical, therefore, that research on antibiotics be extended to enzyme inhibitors that have various pharmacological activities. Thus, the study of low-molecular-weight enzyme inhibitors was initiated by Umezawa (95). Since the discovery of a protease inhibitor was reported in 1969, nearly 50 inhibitors of various enzymes have been found in microbial culture filtrates. Their structures were elucidated, most of them were chemically synthe sized, and new types of structures for inhibition were disclosed. These are reviewed by Umezawa (95-97, 99) and Aoyagi (2, 12). It is often said that the reason microorganisms in nature produce antibi otics is to suppress the growth of the competitors. However, most enzyme inhibitors produced by microorganisms have no significant antimicrobial activity. Moreover, as shown by a study on leupeptin, low-molecular-weight enzyme inhibitors released in culture filtrates are secondary metabolites with no obvious function in the growth of microbial cells. Antibiotics are also secondary metabolites. The genetics of secondary metabolites are being studied in an effort to determine why an almost unlimited number of secondary metabolites of various structures are produced by microorgan isms. Antibiotics can be divided into various groups. Each group contains a common characteristic structural part. Antibiotics of the same group are produced by strains belonging to different species, genera, or families, which indicates a wide distribution of a gene set responsible for the biosynthesis of that characteristic structural moiety. Such common molecular structures display no cytotoxicity. It has been proposed (97) that a gene set directing the biosynthesis of the common structural group was generated whose product is modified to the final products. The final products are released extracellularly. In different strains, the product is modified differently, which results in different final products. It is also possible that such a gene whose product is responsible for the modification was transferred to cells of other strains. Plasmids may have been involved in this transfer. It is possible that numerous genes involved in the biosynthesis of secondary metabolites have been generated in the natural environment and many of them transferred into cells of other strains.