Biosynthesis of Antibacterial Iron-Chelating Tropolones in Aspergillus nidulans as Response to Glycopeptide-Producing Streptomycetes.

Jennifer Gerke,Antje K. Heinrich,Gerhard H. Braus,Verena Große,Anna M. Köhler,Wanping Chen,Jan-Peer Wennrich,Lulu Shao,Helge B. Bode,Frank Surup

doi:10.3389/ffunb.2021.777474

Abstract

The soil microbiome comprises numerous filamentous fungi and bacteria that mutually react and challenge each other by the production of bioactive secondary metabolites. Herein, we show in liquid co-cultures that the presence of filamentous Streptomycetes producing antifungal glycopeptide antibiotics induces the production of the antibacterial and iron-chelating tropolones anhydrosepedonin (1) and antibiotic C (2) in the mold Aspergillus nidulans. Additionally, the biosynthesis of the related polyketide tripyrnidone (5) was induced, whose novel tricyclic scaffold we elucidated by NMR and HRESIMS data. The corresponding biosynthetic polyketide synthase-encoding gene cluster responsible for the production of these compounds was identified. The tropolones as well as tripyrnidone (5) are produced by genes that belong to the broad reservoir of the fungal genome for the synthesis of different secondary metabolites, which are usually silenced under standard laboratory conditions. These molecules might be part of the bacterium-fungus competition in the complex soil environment, with the bacterial glycopeptide antibiotic as specific environmental trigger for fungal induction of this cluster.

Highlights

Soil is a complex and heterogenous ecosystem highly colonized by microorganisms (Karlovsky, 2008)
To unravel the chemical response of A. nidulans toward different Streptomyces species, A. nidulans AGB552 was co-cultivated with S. mobaraensis, S. coelicolor or S. cellulosae on solid and in liquid medium at 30◦C
S. mobaraensis is a known producer of the glycopeptide antibiotic bleomycin, which is active against Aspergilli (Austin et al, 1990; Moore et al, 2003)

Summary

Introduction

Soil is a complex and heterogenous ecosystem highly colonized by microorganisms (Karlovsky, 2008). Microorganisms have developed a chemical arsenal for signaling, defense and protection in multispecies communities (Linares et al, 2006; Scherlach et al, 2013; Granato et al, 2019; Gerke et al, 2020) These low-molecular-weight organic compounds are called secondary metabolites. Two-thirds of antibiotics with natural origin that are valuable in medicine or agriculture are produced by Streptomyces species (Bentley et al, 2002; Chater, 2006). One of those antibiotics is the glycopeptide bleomycin. Streptomyces exhibit a mycelium with aerial filaments that can bear more than 50 spherical airborne spores (Bentley et al, 2002; Chater, 2006; Chater et al, 2010)

Methods

Results

Discussion

Conclusion