Abstract

Microorganisms form diverse multispecies communities in various ecosystems. The high abundance of fungal and bacterial species in these consortia results in specific communication between the microorganisms. A key role in this communication is played by secondary metabolites (SMs), which are also called natural products. Recently, it was shown that interspecies “talk” between microorganisms represents a physiological trigger to activate silent gene clusters leading to the formation of novel SMs by the involved species. This review focuses on mixed microbial cultivation, mainly between bacteria and fungi, with a special emphasis on the induced formation of fungal SMs in co-cultures. In addition, the role of chromatin remodeling in the induction is examined, and methodical perspectives for the analysis of natural products are presented. As an example for an intermicrobial interaction elucidated at the molecular level, we discuss the specific interaction between the filamentous fungi Aspergillus nidulans and Aspergillus fumigatus with the soil bacterium Streptomyces rapamycinicus, which provides an excellent model system to enlighten molecular concepts behind regulatory mechanisms and will pave the way to a novel avenue of drug discovery through targeted activation of silent SM gene clusters through co-cultivations of microorganisms.

Highlights

  • Secondary metabolites (SMs) are low-molecular-mass organic compounds that, unlike primary metabolites, are not directly involved in growth, development or reproduction of the producing organism

  • A more recently developed technique, real-time mass spectrometry, encompassing the techniques of desorption electrospray ionization (DESI) or nanospray desorption electrospray ionization, is a sufficient option in detecting natural products in co-cultivations. An advantage of this method compared to matrix-assisted laser desorption/ionization (MALDI), is that it does not depend on the formation of the matrix and has little to no sample preparation

  • Secondary metabolites are of major interest due to their applicability as therapeutic agents

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Summary

Introduction

Secondary metabolites (SMs) are low-molecular-mass organic compounds that, unlike primary metabolites, are not directly involved in growth, development or reproduction of the producing organism. Microorganisms are able to synthesize a large number of SMs, but the exact number is not known. Mining of microbial genomes revealed the presence of numerous SM gene clusters, displaying a discrepancy between the number of putative genes involved in secondary metabolism and the known SMs in a single microbe (Bergmann et al, 2007; Sanchez et al, 2012; Craney et al, 2013). The model fungus Aspergillus nidulans is potentially able to produce 32 polyketides, 14 non-ribosomal peptides and two indole alkaloids (Brakhage et al, 2008; Rank et al, 2010), with little more than 50% of the produced SMs being identified.

Microbial communication activates secondary metabolites
Functional Analysis of Microbial Communication
The Interaction of Aspergillus with Streptomyces rapamycinicus
Perspectives for the Analysis of Natural Products
Findings
Conclusion

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