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4 Publications visible to you, out of a total of 4
Insect-Associated Bacteria Assemble the Antifungal Butenolide Gladiofungin by Non-Canonical Polyketide Chain Termination.

Abstract (Expand)

Genome mining of one of the protective symbionts ( Burkholderia gladioli ) of the invasive beetle Lagria villosa revealed a cryptic gene cluster coding for the biosynthesis of a novel antifungal … polyketide with a glutarimide pharmacophore. Targeted gene inactivation, metabolic profiling and bioassays led to the discovery of the gladiofungins as yet overlooked components of the antimicrobial armory of the beetle symbiont, specifically against the entomopathogenic fungus Purpureocillium lilacinum . By mutational analyses, isotope labeling and in silico analyses of the modular polyketide synthase, we found that the rare butenolide moiety of gladiofungins derives from an unprecedented polyketide chain termination reaction involving a glycerol-derived C3 building block. The key role of an A-factor synthase (AfsA)-like offloading domain was corroborated by CRISPR-Cas-mediated gene editing, which facilitated the precise excision within a PKS domain.

Authors: S. P. Niehs, J. Kumpfmuller, B. Dose, R. F. Little, K. Ishida, L. V. Florez, M. Kaltenpoth, C. Hertweck

Date Published: 26th Jun 2020

Publication Type: Not specified

Unexpected Bacterial Origin of the Antibiotic Icosalide Two-Tailed Depsipeptide Assembly in Multifarious Burkholderia Symbionts

Abstract (Expand)

Icosalide is an unusual two-tailed lipocyclopeptide antibiotic that was originally isolated from a fungal culture. Yet, its biosynthesis and ecological function have remained enigmatic. By genome mining …g and metabolic pro fi ling of a bacterial endosymbiont (Burkholderia gladioli) of the pest beetle Lagria villosa, we unveiled a bacterial origin of icosalide. Functional analysis of the biosynthetic gene locus revealed an unprecedented nonribosomal peptide synthetase (NRPS) that incorporates two β -hydroxy acids by means of two starter condensation domains in di ff erent modules. This unusual assembly line, which may inspire new synthetic biology approaches, is widespread among many symbiotic Burkholderia species from diverse habitats. Biological assays showed that icosalide is active against entomopathogenic bacteria, thus adding to the chemical armory protecting beetle offspring. By creating a null mutant, we found that icosalide is a swarming inhibitor, which may play a role in symbiotic interactions and bears the potential for therapeutic applications.

Authors: Benjamin Dose, Sarah Niehs, Kirstin Scherlach, Laura V. Florez, Martin Kaltenpoth, Christian Hertweck

Date Published: 30th Aug 2018

Publication Type: Not specified

An antifungal polyketide associated with horizontally acquired genes supports symbiont-mediated defense in Lagria villosa beetles.

Abstract (Expand)

Microbial symbionts are often a source of chemical novelty and can contribute to host defense against antagonists. However, the ecological relevance of chemical mediators remains unclear for most … systems. Lagria beetles live in symbiosis with multiple strains of Burkholderia bacteria that protect their offspring against pathogens. Here, we describe the antifungal polyketide lagriamide, and provide evidence supporting that it is produced by an uncultured symbiont, Burkholderia gladioli Lv-StB, which is dominant in field-collected Lagria villosa. Interestingly, lagriamide is structurally similar to bistramides, defensive compounds found in marine tunicates. We identify a gene cluster that is probably involved in lagriamide biosynthesis, provide evidence for horizontal acquisition of these genes, and show that the naturally occurring symbiont strains on the egg are protective in the soil environment. Our findings highlight the potential of microbial symbionts and horizontal gene transfer as influential sources of ecological innovation.

Authors: L. V. Florez, K. Scherlach, I. J. Miller, A. Rodrigues, J. C. Kwan, C. Hertweck, M. Kaltenpoth

Date Published: 26th Jun 2018

Publication Type: Journal

Chemical warfare between leafcutter ant symbionts and a co-evolved pathogen.

Abstract (Expand)

Acromyrmex leafcutter ants form a mutually beneficial symbiosis with the fungus Leucoagaricus gongylophorus and with Pseudonocardia bacteria. Both are vertically transmitted and actively maintained by … the ants. The fungus garden is manured with freshly cut leaves and provides the sole food for the ant larvae, while Pseudonocardia cultures are reared on the ant-cuticle and make antifungal metabolites to help protect the cultivar against disease. If left unchecked, specialized parasitic Escovopsis fungi can overrun the fungus garden and lead to colony collapse. We report that Escovopsis upregulates the production of two specialized metabolites when it infects the cultivar. These compounds inhibit Pseudonocardia and one, shearinine D, also reduces worker behavioral defenses and is ultimately lethal when it accumulates in ant tissues. Our results are consistent with an active evolutionary arms race between Pseudonocardia and Escovopsis, which modifies both bacterial and behavioral defenses such that colony collapse is unavoidable once Escovopsis infections escalate.

Authors: D. Heine, N. A. Holmes, S. F. Worsley, A. C. A. Santos, T. M. Innocent, K. Scherlach, E. H. Patrick, D. W. Yu, J. C. Murrell, P. C. Vieria, J. J. Boomsma, C. Hertweck, M. I. Hutchings, B. Wilkinson

Date Published: 7th Jun 2018

Publication Type: Journal

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