Extending the “One Strain Many Compounds” (OSMAC) Principle to Marine Microorganisms

Abstract

Genomic data often highlights an inconsistency between the number of gene clusters identified using bioinformatic approaches as potentially producing secondary metabolites and the actual number of chemically characterized secondary metabolites produced by any given microorganism. Such gene clusters are generally considered as “silent”, meaning that they are not expressed under laboratory conditions. Triggering expression of these “silent” clusters could result in unlocking the chemical diversity they control, allowing the discovery of novel molecules of both medical and biotechnological interest. Therefore, both genetic and cultivation-based techniques have been developed aimed at stimulating expression of these “silent” genes. The principles behind the cultivation based approaches have been conceptualized in the “one strain many compounds” (OSMAC) framework, which underlines how a single strain can produce different molecules when grown under different environmental conditions. Parameters such as, nutrient content, temperature, and rate of aeration can be easily changed, altering the global physiology of a microbial strain and in turn significantly affecting its secondary metabolism. As a direct extension of such approaches, co-cultivation strategies and the addition of chemical elicitors have also been used as cues to activate “silent” clusters. In this review, we aim to provide a focused and comprehensive overview of these strategies as they pertain to marine microbes. Moreover, we underline how changes in some parameters which have provided important results in terrestrial microbes, but which have rarely been considered in marine microorganisms, may represent additional strategies to awaken “silent” gene clusters in marine microbes. Unfortunately, the empirical nature of the OSMAC approach forces scientists to perform extensive laboratory experiments. Nevertheless, we believe that some computation and experimental based techniques which are used in other disciplines, and which we discuss; could be effectively employed to help streamline the OSMAC based approaches. We believe that natural products discovery in marine microorganisms would be greatly aided through the integration of basic microbiological approaches, computational methods, and technological innovations, thereby helping unearth much of the as yet untapped potential of these microorganisms.

Microbe-driven chemical ecology: past, present and future

“…Playing with abiotic factors such as nutrients, light, temperature, pH, moisture, salinity and others, one can trigger the expression of genes leading to the production of diverse and novel SMs in terrestrial and marine microorganisms. There are several examples revealing chemical diversity of single isolate by applying different cultivation parameters using so-called OSMAC (one strain-many compounds) approach [21] [22]. Molecular mechanisms of SM regulation by nutrients are best-described for major nutrient sources, such as carbon, nitrogen, phosphate and a few selected micronutrients, such as the trace metals like iron, copper, and zinc (reviewed in [23,24]).…”

Anthracycline Shunt Metabolites From Philippine Marine Sediment-Derived Streptomyces Destroy Cell Membrane Integrity of Multidrug-Resistant Staphylococcus aureus

“…Members of the genus Streptomyces of the phylum Actinobacteria are soil saprophytes that are known producers of antibiotics (Shaik et al, 2017;Yang and Song, 2017;Kemung et al, 2018;Yang et al, 2020). These microorganisms contain high GC content in their DNA sequences and are reported to have antibiotic-producing biosynthetic gene clusters (BGC) (Hopwood, 2007;Dhakal et al, 2017;Romano et al, 2018) that produces about 75% of the clinically available antibacterial drugs in the market (Kemung et al, 2018). However, in the last 20 years, the re-discovery of previously characterized bioactive compounds and strain redundancy decreased the interest in these soil-dwelling bacteria as a source of novel bioactive compounds (Yang and Song, 2017;Almeida et al, 2019).…”

“…However, in the last 20 years, the re-discovery of previously characterized bioactive compounds and strain redundancy decreased the interest in these soil-dwelling bacteria as a source of novel bioactive compounds (Yang and Song, 2017;Almeida et al, 2019). Thus, Streptomyces living in other niches, such as the marine environment, gained value because of their chemodiversity (Chelvan et al, 2016;Dhakal et al, 2017;Yang and Song, 2017;Kemung et al, 2018;Romano et al, 2018;Al-Dhabi et al, 2019;Almeida et al, 2019).…”

Activation and enhancement of Caerulomycin A biosynthesis in marine-derived Actinoalloteichus sp. AHMU CJ021 by combinatorial genome mining strategies

“…However, the production of bioactive secondary metabolites in marine actinomycetes is always hampered due to unavailable expression of their biosynthetic gene clusters (BGCs) under laboratory conditions [8,10,11]. To unlock the biosynthesis potential of these strains, the innovative genome mining strategyribosome engineering is adopted to activate the expression of essential biosynthetic genes of cryptic secondary metabolites in strain's genome [12][13][14][15][16][17][18].…”