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Sarah Niehs

About Sarah Niehs:
No description specified

SEEK ID: https://data.chembiosys.de/people/111

Location:  Germany

Expertise: Structure Elucidation, Fermentation, Microbiology, Chemical Ecology

Tools: MS/MS, LC/MS, Fermentation, NMR

ORCID: https://orcid.org/0000-0002-2012-5949

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Total ChemBioSys
No description specified

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B1

Cryptic Mediators at the Bacterial-Fungal Interface: Mushroom Soft Rot Diseases as
Infection Model

Public web page: Not specified

Food-poisoning Bacteria and their Chemical Arsenal
Total ChemBioSys, B1

Burkholderia gladioli, cocovenenans, food-poisoning, tempeh, bonkrekic, acid, chemical, Natural Products

Snapshots: No snapshots

Chemical Ecology of Insect Symbionts
B1

Natural Products, Structure Elucidation, Burkholderia, gladioli, Lagria, villosa, insect symbiont, protective symbiosis

Snapshots: No snapshots

Natural Products of Endofungal Symbionts (Rhizopus-Mycetohabitans Interaction)
B1

Natural Products, Endosymbionts, Rhizopus microsporus, Mycetohabitans, Structure Elucidation, Symbiosis

Snapshots: No snapshots

22 hidden items
NMR data bolagladin B
Total ChemBioSys, B1
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Creator: Sarah Niehs

Submitter: Sarah Niehs

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NMR data gladiofungin A
B1
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Creator: Sarah Niehs

Submitter: Sarah Niehs

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NMR data necroxime A
B1
No description specified

Creator: Sarah Niehs

Submitter: Sarah Niehs

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NMR data endopyrrole A
B1
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Creator: Sarah Niehs

Submitter: Sarah Niehs

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NMR data icosalide A1
B1
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Creator: Sarah Niehs

Submitter: Sarah Niehs

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Food-Poisoning Bacteria Employ a Citrate Synthase and a Type II NRPS To Synthesize Bolaamphiphilic Lipopeptide Antibiotics.
Total ChemBioSys, B1

Abstract (Expand)

Mining the genome of the food-spoiling bacterium Burkholderia gladioli pv. cocovenenans revealed five nonribosomal peptide synthetase (NRPS) gene clusters, including an orphan gene locus (bol). Gene … inactivation and metabolic profiling linked the bol gene cluster to novel bolaamphiphilic lipopeptides with antimycobacterial activity. A combination of chemical analysis and bioinformatics elucidated the structures of bolagladin A and B, lipocyclopeptides featuring an unusual dehydro-beta-alanine enamide linker fused to an unprecedented tricarboxylic fatty acid tail. Through a series of targeted gene deletions, we proved the involvement of a designated citrate synthase (CS), priming ketosynthases III (KS III), a type II NRPS, including a novel desaturase for enamide formation, and a multimodular NRPS in generating the cyclopeptide. Network analyses revealed the evolutionary origin of the CS and identified cryptic CS/NRPS gene loci in various bacterial genomes.

Authors: B. Dose, C. Ross, S. P. Niehs, K. Scherlach, J. P. Bauer, C. Hertweck

Date Published: 11th Aug 2020

Publication Type: Not specified

Insect-Associated Bacteria Assemble the Antifungal Butenolide Gladiofungin by Non-Canonical Polyketide Chain Termination.
Total ChemBioSys, B1

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

Mining Symbionts of a Spider-Transmitted Fungus Illuminates Uncharted Biosynthetic Pathways to Cytotoxic Benzolactones
Total ChemBioSys, B1

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
Total ChemBioSys, B1

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
Total ChemBioSys, B1

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

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