Simon Sieber

Simon Sieber
University of Zurich | UZH · Chemistry

PhD

About

33
Publications
4,086
Reads
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274
Citations
Introduction
Natural products possess complex structures and their potential for drug discovery has been well recognized. My research focuses on the development of new analytical tools to improve and optimize the isolation and structure elucidation of novel active compounds. My field of research is located at the interface with chemical biology, and organic and analytical chemistry.
Additional affiliations
November 2016 - present
University of Zurich
Position
  • Research Associate
November 2015 - October 2016
ETH Zurich
Position
  • PostDoc Position
April 2011 - July 2015
University of Basel
Position
  • PhD candidate, NCCR Chemical Biology

Publications

Publications (33)
Article
Full-text available
Pseudomonas syringae is an important plant pathogen of many valuable crops worldwide, with more than 60 identified pathovars. The phytotoxins produced by these organisms were related to the severity of the damage caused to the plant. An emerging strategy to treat bacterial infections relies on interference with their signaling systems. In this stud...
Article
Full-text available
Bacterial and viral infections pose a direct threat to human health due to the increase of drug-resistant and novel pathogenic strains. Natural products represent a prolific source of bioactive metabolites, which have been exploited for their therapeutic effects. In particular, cyanobacteria were identified as important producers of secondary metab...
Article
The toxicity of the cyanobacterium Microcystis aeruginosa EAWAG 127a was evaluated against the sensitive grazer Thamnocephalus platyurus, and the extract possessed strong activity. To investigate the compounds responsible for cytotoxicity, a series of peptides from this cyanobacterium were studied using a combined genomic and molecular networking a...
Article
Full-text available
Antimicrobial resistance in pathogenic bacteria is considered a major public health issue necessitating the discovery of alternative antimicrobial compounds. In this regard, targeted genome mining in bacteria occupying under-explored ecological niches has the potential to reveal such compounds, including bacteriocins. In this study, we determined t...
Article
Full-text available
Cell-surface display systems are biotechnological techniques used to express heterologous proteins on the cell surface. Their application depends directly on the cell system used, as well as on the anchoring point for the surface displayed protein. To meet most application demands an inexpensive, safe, and scalable production platform, that reduces...
Article
Full-text available
After a century of investigations, the function of the obligate betaproteobacterial endosymbionts accommodated in leaf nodules of tropical Rubiaceae remained enigmatic. We report that the α-d-glucose analogue (+)-streptol, systemically supplied by mature Ca.Burkholderia kirkii nodules to their Psychotria hosts, exhibits potent and selective root gr...
Preprint
Full-text available
Cell-surface display systems are biotechnological techniques used to expose heterologous proteins on the cell surface. Their application depends directly on the cell system used for the development, as well as anchoring point surface displayed protein. To meet most application demands an inexpensive, safe, and scalable production platform, that red...
Article
Full-text available
The open innovation hub Digital Health and Patient Safety Platform (DHPSP) was recently established with the purpose to invigorate collaborative scientific research and the development of new digital products and personalized solutions aiming to improve human health and patient safety. In this study, we evaluated the effectiveness of a Twitter-base...
Preprint
Full-text available
Pseudomonas syringae is an important pathogen of many agriculturally valuable crops. Among the various pathovars described P. syringae pv. syringae (Pss) has a particularly wide host range, infecting primarily woody and herbaceous host plants. The ability of Pss to cause bacterial apical necrosis of mango trees is dependent on the production of the...
Article
Full-text available
New strategies to efficiently treat bacterial infections are crucial to circumvent the increase of resistant strains and to mitigate side effects during treatment. Skin and soft tissue infections represent one of the areas suffering the most from these resistant strains. We developed a new drug delivery system composed of the green algae, Chlamydom...
Preprint
Pseudomonas syringae is an important pathogen of many agriculturally valuable crops. Among the various pathovars described P. syringae pv. syringae (Pss) has a particularly wide host range, infecting primarily woody and herbaceous host plants. The ability of Pss to cause bacterial apical necrosis of mango trees is dependent on the production of the...
Preprint
div> Pseudomonas syringae is an important pathogen of many agriculturally valuable crops. Among the various pathovars described P. syringae pv. syringae (Pss) has a particularly wide host range, infecting primarily woody and herbaceous host plants. The ability of Pss to cause bacterial apical necrosis of mango trees is dependent on the production...
Article
Full-text available
The C7N-aminocyclitol kirkamide was recently isolated from the plant obligate symbiont Candidatus Burkholderia kirkii and was hypothesized to be beneficial to the plant host due to its cytotoxic activity against insects and arthropods. To study its mechanism of action and inspired by its structural similarity with N-acetylglucosamine (GlcNAc) and o...
Article
Full-text available
We designed and engineered a dye production cassette encoding a heterologous pathway, including human tyrosine hydroxylase and Amanita muscaria 4,5-DOPA dioxygenase, for the biosynthesis of the betaxanthin family of plant and fungal pigments in mammalian cells. The system does not impair cell viability, and can be used as a non-protein reporter sys...
Article
Full-text available
We report the synthesis and first characterisation of the novel chemical probe 3-bromotetrazine and establish its reactivity towards nucleophiles leading to the synthesis of several novel classes of 3-monosubstituted s-tetrazines. A remarkable functional group selectivity is observed and is utilised to site-selectively functionalise different compl...
Article
Only a few natural products possessing a diazeniumdiolate have been isolated and usually these compounds display a broad range of biological activities. Only recently the first diazeniumdiolate natural product biosynthetic gene cluster was identified in Burkholderia cenocepacia H111, which produces the fungicide (—)‐fragin and the signal molecule (...
Preprint
div> We report the synthesis of the novel precursor 3-bromotetrazine and its successful use in the synthesis of various families of 3-monosubstituted s-tetrazines. A remarkable functional group selectivity is utilized to site-selectively functionalize different complex molecules. The unexpected stability of 3- bromotetrazine in aqueous media facil...
Article
Full-text available
Many social behaviours of bacteria are regulated by quorum sensing through the production and perception of structurally diverse signal molecules. The opportunistic pathogen Burkholderia cenocepacia uses classic N-acyl-homoserinlactones and cis-2-unsatturated fatty acids for communication. A recent study has identified an additional signal, valdiaz...
Article
The plant Psychotria kirkii hosts an obligatory bacterial symbiont, Candidatus Burkholderia kirkii, in nodules on their leaves. Recently, a glucosylated derivative of (+)‐streptol, (+)‐streptol glucoside, was isolated from the nodulated leaves and was found to possess a plant growth inhibitory activity. To establish a structure activity relationshi...
Article
Full-text available
Members of the diazeniumdiolate class of natural compounds show potential for drug development because of their antifungal, antibacterial, antiviral, and antitumor activities. Yet, their biosynthesis has remained elusive to date. Here, we identify a gene cluster directing the biosynthesis of the diazeniumdiolate compound fragin in Burkholderia ceno...
Article
Full-text available
Bacteria of the genus Burkholderia establish an obligate symbiosis with plant species of the Rubiaceae and Primulaceae families. The bacteria, housed within the leaves, are transmitted hereditarily and have not yet been cultured. We have sequenced and compared the genomes of eight bacterial leaf nodule symbionts of the Rubiaceae plant family. All o...
Article
The new C7 N aminocyclitol kirkamide (1) was isolated from leaf nodules of the plant Psychotria kirkii by using a genome-driven (1) H NMR-guided fractionation approach. The structure and absolute configuration were elucidated by HRMS, NMR, and single-crystal X-ray crystallography. An enantioselective total synthesis was developed, which delivered k...
Article
The isolation and structural characterization of three new heterocyclic and macrocyclic peptides, balgacyclamides A-C, from Microcystis aeruginosa EAWAG 251 are reported. The constitutions were determined by 2D-NMR methods and mass spectrometry, and the configurations were assigned after ozonolysis and hydrolysis by HPLC-MS methods using Marfey's m...
Article
Full-text available
Chemical compounds isolated from natural sources offer unique opportunities to understand life on a molecular level. In this account, an overview over different natural products investigated in our research group over the last decade is presented. We have shown that protein localization in living cells can be controlled by anguinomycins and derivat...

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Project
Website: http://inpst.net/ Twitter: https://twitter.com/_INPST Facebook: https://www.facebook.com/INPST/ The International Natural Product Sciences Taskforce (INPST) represents an open innovation platform bringing together scientists and key opinion leaders of the natural product scientific research field, as well as members of multiple scientific excellence centers and pharmaceutical-, biotech-, and natural product-related industries.