Doctoral Candidates (DC)

DC1 Judit Szenei

Project title: Natural Products Structure Prediction based on Genomic Data

Description: Using genomic data to assess the potential of microorganisms to biosynthesize natural products with applications in medicine, biotechnology, agriculture, or foods in the recent years has tremendously progressed. The genome mining platform antiSMASH, which is an Open Source project coordinated at DTU and WUR with many international collaborators currently is the leading software to mine genome data for the presence of natural products biosynthetic pathways. antiSMASH can detect 81 different types of biosynthetic gene clusters (BGCs) from genomic data, but currently can only provide rough product structure predictions for a handful of these BGC types. This project aims to build a new approach how antiSMASH can model chemical compounds in-memory and apply any modifications to the core structure from predicted tailoring reactions, utilizing what is currently known about clusters and product structures in e.g. the MIBiG database.

Email: szenei@biosustain.dtu.dk

DC2 Annette Lien

Project title: Identifying and visualising shared building blocks within biosynthetic gene clusters

Description: Building new tools for the analysis of shared building blocks within biosynthetic gene clusters (BGCs) and connecting them to metabolite substructures and their associated metabolome peak patterns.

Email: annette.lien@wur.nl

DC3 Aleksandra Korenskaia

Project title: PhyloNaP: a user-friendly webtool that facilitates structure prediction of natural products based on fine-scale gene phylogeny

Description: This project involves creating a comprehensive database of phylogenetic trees for tailoring enzymes. The database will include both proteins for which the catalyzed reaction (substrate-product information) is known and those that are not well annotated. Based on it, a user-friendly web tool will be developed to assist researchers in classifying their biosynthetic enzymes phylogenetically and predicting substrate and enzymatic transformation reactions.

Email: aleksandra.korenskaia@uni-tuebingen.de

DC4 Lisa Vader

Project title: Improved Fungal BGC Predictions and Analyses for antiSMASH and antiSMASH-DB

Description: Using genomic data to assess the potential of microorganisms to biosynthesize natural products with applications in medicine, biotechnology, agriculture, or foods in the recent years has tremendously progressed. The genome mining platform antiSMASH, which is an Open Source project coordinated at DTU and WUR with many international collaborators currently is the leading software to mine genome data for the presence of natural products biosynthetic pathways. Due to much higher abundance of bacterial genome data a lot of improvements in antiSMASH have been targeting bacterial biosynthetic gene clusters (BGCs). Leveraging on the huge expertise of DTU in fungal natural products biosynthesis, this thesis aims to develop novel modules for antiSMASH to improve the detection and especially analysis/interpretation of fungal BGCs.

Email: lisvad@biosustain.dtu.dk

DC5 Rosina Torres Ortega

Project title: Substructure-driven linking of Genes and Metabolites to accelerate Natural Products Discovery

Description: Improve the current metabolomics workflows, using unsupervised machine learning algorithms for substructure discovery and linking the metabolomics with genomics for Natural Product discovery.

Email: rosina.torresortega@wur.nl

DC6 Caleb Damas Ramos

Project title: Large-scale genome mining for Streptomyces BGCs

Description: The Natural Products Genome Mining group at DTU Biosustain has sequenced over 1200 actinomycetal strains, an unprecedented treasure trove for yet unstudied biosynthetic gene clusters and their products. During my PhD, I’ll exploit this data following 3 main subtasks. First, systematic mining of the sequence data using genome mining tools like antiSMASH, ARTS 2.0, BGCFlow, and the new ones developed by other MAGic-MOLFUN doctoral candidates. Then, we will select novel biosynthetic gene clusters (BGCs) and clone them using the most advanced synthetic biology techniques for actinomycetes. Finally, we will transfer the BGCs to suitable Streptomyces expression hosts and monitor their products using HPLC-HRMS.

Email: luiram@biosustain.dtu.dk

DC7 Gioele Pecin

Project title: Boosting the discovery of novel fungal natural products

Description: Fungal metabolites are an underexplored niche of chemical diversity for the discovery of new natural products, and among them cyclic peptides and depsipeptides represent one of the best known classes of bioactive fungal metabolites. The understanding of how fungi nonribosomal peptide synthases (NRPS) synthesize these molecules has expanded in the last decade with continuous new insights from the analysis of new genomes and biosynthetic gene clusters (BGCs), that frequently cluster NRPS with other polyketide and prenyl transferases. With the purpose to develop tools to untap new fungal peptides produced by minor species from MEDINA collection, the work will be focused on three different fungal cyclic lipopeptides and depsipeptides to be used as model systems from distant fungal lineages. The work will involve the study of the physiology and fermentation requirements of these molecules to identify growth limiting factors, and best production conditions. The use of omics tools will include a metabolome analysis of the strains will help to infer potential new metabolites from metabolomic networking, that will be correlated with high quality annotated fungal genome sequences of these species and new proposed BGCs for the small molecules of interest, and in particular for the biosynthesis of the three different targeted lipopeptides.

Email: gioele.pecin@medinaandalucia.es

DC8 Dora Ferreira

Project Titel: Uncovering the biosynthetic potential of a rare actinomycetes genus coupling genomics and metabolomics data

Description: Development of tool(s) for assessment of the genomic and metabolic potential of a rare group of actinomycetes; selection and isolation of structurally interesting compounds to validate the developed tool(s). The main goal of this project is the development of tool(s) that allow the quick assessment of the genomic and metabolic potential of a rare group of actinomycetes. This coupling of genomic and metabolomic data will enable prioritization of the strains based on their chemical/molecular novelty, and structurally relevant compounds will be selected, isolated, and their structure elucidated, to validate the developed tool(s).

E-mail: dferreira@naicons.com

DC9 Shreyash Pramod Borkar

Project Title: Development of a screening platform for functional bioactive molecules by enzyme and pathway mining.

Description: The focus is on the development of methods for identification, prediction and screenings of enzymes and enzymatic pathways in silico and in vitro. Next generation sequencing and bioinformatics techniques are to be used for the creation of in-silico enzyme and pathway libraries. Followed by development of high-throughput cloning methods to convert the in-silico generated libraries into screenable in-vitro libraries. The resulting libraries would be screened for desired enzymatic activities or, if possible, even directly for functional bioactive molecules.

Email: shreyash.borkar@c-lecta.com

DC10 Luca Salvi

Project title: Identification of novel secondary metabolites from rare actinomycetes

Description: Rare actinomycetes from NAICONS and Tübingen strain collection will be used to isolate novel natural products through the application of state-of-the-art methods such as 1) expression of BGCs of interest in a heterologous host (e.g. Streptomyces coelicolor, Streptomyces albus, Amycolatopsis japonicum); 2) deletion or overexpression of negative/positive regulators of BGCs; 3) optimization of the precursors supply by using metabolic engineering approaches; 4) purification of interesting compounds by chromatographic techniques, and structural elucidation and determination of biological activity.

Email: luca.salvi@uni-tuebingen.de

DC11 Adriana Romero

Project title: Fungal matabolomics to link metabolites to their genes

Description: Fungi are well recognized for their ability to produce a wide variety of secondary metabolites. This can benefit humans in the food, pharmaceutical and agrochemical industries. However, they are also able to produce some harmful toxins. This project aims to link fungi metabolites with their biosynthetic gene clusters (BGCs). Enabling fungal strains assessment as producers of mycotoxins and interesting natural products, such as pigments. This will be done by combining matabolomic and genome mining techniques.

Email: aromero@biosustain.dtu.dk

DC12 Artem Fetter

Project title: Development of an integrated biomapping metabologenomics workflow for accelerated antibiotic discovery from rare actinomycetes

Description: In my research, I am focusing on the prioritization of rare actinomycete strains through the combined use of phylogenomic and BGC genome mining approaches. The prioritized strains, will be cultured in miniaturized microcosm cocultures to maximize chemical diversity, followed by a systematic comparative metabolomics analysis. A structured bioactivity mapping (biomapping) procedure wil be approached to analyze metabolite extracts with known antibiotic profiles. Utilizing NPLinker, I am going to establish connections between metabolites and their corresponding BGCs, enhancing our understanding of microbial interactions. The integration of metabologenomic data with bioactivity mapping is part of the ongoing effort to expand the NPLinker framework systematically. This approach provides a more comprehensive exploration of the relationships between genomics and metabolomics. In later stages, my focus is on the prioritization and purification of identified antibiotics from novel biosynthetic and chemical spaces.

Email: artem.fetter@strath.ac.uk