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4 Publications visible to you, out of a total of 4
Mining Symbionts of a Spider-Transmitted Fungus Illuminates Uncharted Biosynthetic Pathways to Cytotoxic Benzolactones

Abstract (Expand)

A spider-transmitted fungus (Rhizopus microspo- rus) that was isolated from necrotic human tissue was found to harbor endofungal bacteria (Burkholderia sp.). Metabolic profiling of the symbionts revealed … a complex of cytotoxic agents (necroximes). Their structures were characterized as oxime-substituted benzolactone enamides with a peptidic side chain. The potently cytotoxic necroximes are also formed in symbiosis with the fungal host and could have contributed to the necrosis. Genome sequencing and computational analyses revealed a novel modular PKS/NRPS assembly line equipped with several non-canonical domains. Based on gene-deletion mutants, we propose a biosynthetic model for bacterial benzolactones. We identified specific traits that serve as genetic handles to find related salicylate macrolide pathways (lobata- mide, oximidine, apicularen) in various other bacterial genera. Knowledge of the biosynthetic pathway enables biosynthetic engineering and genome-mining approaches.

Authors: Sarah Niehs, Benjamin Dose, Sophie Richter, Sacha J. Pidot, Timothy P. Stinear, Hans-Martin Dahse, Christian Hertweck

Date Published: 10th Feb 2020

Publication Type: Not specified

Genome Mining Reveals Endopyrroles from a Nonribosomal Peptide Assembly Line Triggered in Fungal-Bacterial Symbiosis

Abstract (Expand)

The bacterial endosymbiont (Burkholderia rhizoxinica) of the rice seedling blight fungus (Rhizopus microsporus) harbors a large number of cryptic biosynthesis gene clusters. Genome mining and sequence … similarity networks based on an encoded nonribosomal peptide assembly line and the associated pyrrole- forming enzymes in the symbiont indicated that the encoded metabolites are unique among a large number of tentative pyrrole natural products in diverse and unrelated bacterial phyla. By performing comparative metabolic pro fi ling using a mutant generated with an improved pheS Burkholderia counterselection marker, we found that the symbionts ’ biosynthetic pathway is mainly activated under salt stress and exclusively in symbiosis with the fungal host. The cryptic metabolites were fully characterized as novel pyrrole-substituted depsipeptides (endopyrroles). A broader survey showed that endopyrrole production is a hallmark of geographically distant endofungal bacteria, which produce the peptides solely under symbiotic conditions.

Authors: Sarah Niehs, Benjamin Dose, Kirstin Scherlach, Sacha J. Pidot, Timothy P. Stinear, Christian Hertweck

Date Published: 8th Jul 2019

Publication Type: Not specified

Genomics-driven discovery of a linear lipopeptide promoting host colonization by endofungal bacteria

Abstract (Expand)

The rice seedling blight fungus Rhizopus microsporus weakens or kills plants by means of a potent toxin produced by endobacteria (Burkholderia rhizoxinica) that live within the fungal hyphae. The success … of the highly attuned microbial interaction is partly based on the bacteria ’ s ability to roam and re-colonize the fungal host. Yet, apart from the toxin, chemical mediators of the symbiosis have remained elusive. By genome mining and comparison we identi fi ed a cryptic NRPS gene cluster that is conserved among all sequenced Rhizopus endosymbionts. Metabolic pro fi ling and targeted gene inactivation led to the discov- ery of a novel linear lipopeptide, holrhizin A, which was fully characterized. Through in vitro and in vivo assays we found that holrhizin acts (A) as a biosurfactant to reduce surface tension, (B) in fl uences the for- mation of mature bio fi lms and thus cell motility behavior that ultimately supports the bacterial cells to (C) colonize and invade the fungal host, consequently supporting the re-establishment of the exceptional Burkholderia-Rhizopus symbiosis. We not only unveil structure and function of an linear lipopeptide from endofungal bacteria but also provide a functional link between the symbiont’ s orphan NRPS genes and a chemical mediator that promotes bacterial invasion into the fungal host.

Authors: Sarah Niehs, Kirstin Scherlach, Christian Hertweck

Date Published: 31st Aug 2018

Publication Type: Not specified

Genomics-Driven Discovery of a Symbiont-Specific Cyclopeptide from Bacteria Residing in the Rice Seedling Blight Fungus

Abstract (Expand)

The rice seedling blight fungus Rhizopus microsporus harbors endosymbiotic bacteria (Burkholderia rhizoxinica) that produce the virulence factor rhizoxin and control host development. Genome mining … indicated a massive inventory of cryptic non- ribosomal peptide synthetase (NRPS) genes, which have not yet been linked to any natural products. The discovery and full characterization of a novel cyclopeptide from endofungal bac- teria is reported. In silico analysis of an orphan, symbiont-spe- cific NRPS predicted the structure of a nonribosomal peptide, which was targeted by LC-MS/MS profiling of wild-type and engineered null mutants. NMR spectroscopy and chemical deri- vatization elucidated the structure of the bacterial cyclopep- tide. Phylogenetic analyses revealed the relationship of starter C domains for rare N-acetyl-capped peptides. Heptarhizin is produced under symbiotic conditions in geographically con- strained strains from the Pacific clade; this indicates a potential ecological role of the peptide.

Authors: Sarah Niehs, Benjamin Dose, Kirstin Scherlach, Martin Roth, Christian Hertweck

Date Published: 16th Aug 2018

Publication Type: Not specified

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