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

Abstract

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.

Metabolomic profiles of the liquid state fermentation in co-culture of Eurotium amstelodami and Bacillus licheniformis

“…Here, we propose a strategy to screen co-culture microbial combinations by targeting the improvement of antibacterial activity. Interestingly, studies have shown that changes in state of the medium (i.e., solid or liquid), composition (i.e., carbon source and nitrogen source) and culture conditions (i.e., temperature, culture length, and pH), or the addition of some trace elements might lead to improved antibacterial activity ( Boruta et al, 2020 ; Boruta, 2021 ; Gao et al, 2021 ; Sun et al, 2022 ), which provided new strategies to further explore valuable SMs of the co-culture of E. amstelodami and Bacillus species.…”

Modern Trends in Natural Antibiotic Discovery

“…Unconventional methods are needed to awaken “silent” biosynthetic pathways and induce the production of secondary metabolites. One of the most promising approaches to in vitro cultivation is simulation of the natural interaction between different species of microorganisms by means of co-culturing [ 52 ] to obtain a large variety of secondary metabolites [ 53 ]. In a co-culture, two or more distinct microorganisms are incubated together in order to mimic the natural environment [ 52 , 54 , 55 ].…”

Tunable population dynamics in a synthetic filamentous coculture

“…Although these biotic induction methods have proven to be fruitful, most studies have been undertaken in a random or empirical manner. Different strains are often simply combined in shake flask cultures, using rich standard cultivation media for Streptomyces sp., as reviewed by Boruta (2021), Maglangit et al (2020), Wakefield et al (2017), and Yu et al (2019). However, in the natural environment, nutrients are typically not very abundant and the resulting nutrient availability greatly influences specialized metabolite production (Doull & Vining, 1990;Scherlach et al, 2011).…”