A bioprocess perspective on the production of secondary metabolites by Streptomyces in submerged co-cultures

Filamentous microorganisms are potent sources of bioactive secondary metabolites, the molecules formed in response to complex environmental signals. The chemical diversity encoded in microbial genomes is only partially revealed by following the standard microbiological approaches. Mimicking the natural stimuli through laboratory co-cultivation is one of the most effective methods of awakening the formation of high-value metabolic products. Whereas the biosynthetic outcomes of co-cultures are reviewed extensively, the bioprocess aspects of such efforts are often overlooked. The aim of the present review is to discuss the submerged co-cultivation strategies used for triggering and enhancing secondary metabolites production in Streptomyces, a heavily investigated bacterial genus exhibiting an impressive repertoire of secondary metabolites, including a vast array of antibiotics. The previously published studies on influencing the biosynthetic capabilities of Streptomyces through co-cultivation are comparatively analyzed in the bioprocess perspective, mainly with the focus on the approaches of co-culture initiation, the experimental setup, the design of experimental controls and the ways of influencing the outcomes of co-cultivation processes. These topics are discussed in the general context of secondary metabolites production in submerged microbial co-cultures by referring to the Streptomyces-related studies as illustrative examples.