Today, the frequency of discovery of new antibiotics in microbial culture is significantly decreasing. The evidence from whole-genome surveys suggests that many genes involved in the synthesis of unknown metabolites do exist but are not expressed under conventional cultivation conditions. Therefore, it is urgently necessary to study the conditions that make otherwise silent genes active in microbes. Here we overview the knowledge on the antibiotic production promoted by cocultivation of multiple microbial strains. Accumulating evidence indicates that cocultivation can be an effective way to stimulate the production of substances that are not formed during pure cultivation. Characterization of the promotive factors produced by stimulator strains is expected to give clues to the development of effective cultivation conditions for drug discovery. The Journal of Antibiotics (2017) 70, 361-365; doi:10.1038/ja.2016; published online 19 October 2016
INTRODUCTIONEver since the discovery of penicillin, antibiotics and many other kinds of biologically active substances have been obtained from microbial cultures. The divergent actions of these compounds have contributed to the current knowledge of the basic mechanisms of molecular interaction and therapeutic methods as well. This special issue contains studies dealing with the milestone works that have advanced the development of basic biological sciences and medicinal applications.In contrast to the great successes in mining of useful natural products in the last century, the frequency of isolation of new compounds from microbial cultures is substantially decreasing in this century. 1 In accordance with this situation, the pharmaceutical industry is changing the direction of drug development and reducing the weight of natural products among the resources for screening.The factors limiting the chances of new discovery can be attributed to humans, not to microorganisms. Studies on the accumulating genomic information indicate that a large number of biosynthetic gene clusters are not expressed under the conventional culture conditions. 1,2 Namely, the potential diversity of microbial products is still large, but scientists do not yet know how to fully take advantage of the abilities of microbes. This problem is due in part to the fact that the methods of modern microbiology still depend on the manipulation techniques developed by Robert Koch and colleagues, which relies on the single-colony isolation from solid agar plates and subsequent pure cultivation under laboratory conditions. We can imagine that the dependence on those artificial conditions restricts access to a number of microorganisms and/or their abilities.To address the issue, attempts have been made to discover new substances specifically produced in coculture. In natural environments, microbes are living in diverse associations with other organisms. The modes of interaction include antagonism, commensalism and mutualism. Functions specifically correlating with such interactions may not get activated during conv...