Title Participants Abstract "Tuning the antimicrobial activity of microbial glycolipid biosurfactants through chemical modification" "Melike Pala, Martijn Castelein, Camille Dewaele, Sophie Roelants, Wim Soetaert, Christian Stevens" "Sophorolipids, glycolipid biosurfactants derived from microorganisms such as Starmerella bombicola, possess distinctive surface-active and bioactive properties, holding potential applications in cosmetics, pharmaceuticals and bioremediation. However, the limited structural variability in wild-type sophorolipids restricts their properties and applications. To address this, metabolic engineering efforts have allowed to create a portfolio of molecules. In this study, we went one step further by chemically modifying microbially produced sophorosides, produced by an engineered S. bombicola. Twenty-four new sophoroside derivatives were synthesized, including sophoroside amines with varying alkyl chain lengths (ethyl to octadecyl) on the nitrogen atom and their corresponding quaternary ammonium salts. Additionally, six different microbially produced glycolipid biosurfactants were hydrogenated to achieve fully saturated lipid tails. These derivatives, along with microbially produced glycolipids and three benchmark biosurfactants (di-rhamnolipids, alkyl polyglucosides, cocamidopropyl betaine), were assessed for antimicrobial activity against bacteria (Bacillus subtilis, Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, Pseudomonas aeruginosa) and yeast (Candida albicans). Results indicated that microbially produced glycolipids, such as bola sophorosides, acidic sophorolipids and acidic glucolipids exhibit selective antimicrobial activity against the test organisms. Conversely, lactonic sophorolipids, sophoroside amines and quaternary ammonium salts display a broad antimicrobial activity. N-octyl, N-dodecyl and N-octadecyl derivatives exhibit the lowest minimal inhibitory concentrations, ranging from 0.014 to 20.0 mg mL−1. This study demonstrates the potential synergy of thoughtful biotechnology and targeted chemistry to precisely tailor glycolipid biosurfactants to meet specific requirements across applications." "Glioblastoma-associated mesenchymal stem/stromal cells and cancer-associated fibroblasts : partners in crime?" "Thibault Lootens, Bart Roman, Christian Stevens, Olivier De Wever, Robrecht Raedt" "Tumor-associated mesenchymal stem/stromal cells (TA-MSCs) have been recognized as attractive therapeutic targets in several cancer types, due to their ability to enhance tumor growth and angiogenesis and their contribution to an immunosuppressive tumor microenvironment (TME). In glioblastoma (GB), mesenchymal stem cells (MSCs) seem to be recruited to the tumor site, where they differentiate into glioblastoma-associated mesenchymal stem/stromal cells (GA-MSCs) under the influence of tumor cells and the TME. GA-MSCs are reported to exert important protumoral functions, such as promoting tumor growth and invasion, increasing angiogenesis, stimulating glioblastoma stem cell (GSC) proliferation and stemness, mediating resistance to therapy and contributing to an immunosuppressive TME. Moreover, they could act as precursor cells for cancer-associated fibroblasts (CAFs), which have recently been identified in GB. In this review, we provide an overview of the different functions exerted by GA-MSCs and CAFs and the current knowledge on the relationship between these cell types. Increasing our understanding of the interactions and signaling pathways in relevant models might contribute to future regimens targeting GA-MSCs and GB-associated CAFs to inhibit tumor growth and render the TME less immunosuppressive." "Straightforward synthesis of P-alkylphosphonamidates and bioactivity screening as herbicides or quorum sensing modulators" "Simon Backx, Andreas Dejaegere, Andreas Simoens, Jef Van de Poel, Dorota Krasowska, Emmelie De Ridder, Christian Stevens" "Triethylamine-mediated transformation of phosphonates into phosphonamidates" "Simon Backx, Andreas Dejaegere, Andreas Simoens, Jef Van de Poel, Dorota Krasowska, Christian Stevens" "pySODM : simulating and optimizing dynamical models in Python 3" "Tijs Alleman, Christian Stevens, Jan Baetens" "In this work we present our generic framework to construct, simulate and calibrate dynamical systems in Python 3. Its goal is to reduce the time it takes to implement a dynamical system with -dimensional states represented by coupled ordinary differential equations (ODEs), simulate the system deterministically or stochastically, and, calibrate the system using -dimensional data. We demonstrate our code’s capabilities by building three models in the context of two case studies. First, we forecast the yields of the enzymatic esterification reaction of D-glucose and lauric acid, performed in a continuous-flow, packed-bed reactor. The model yields a satisfactory description of the reaction yields under different flow rates and can be applied to design a viable process. Second, we build a stochastic, age-stratified model to make forecasts on the evolution of influenza in Belgium during the 2017–2018 season. Using only limited data, our simple model was able to make a fairly accurate assessment of the future course of the epidemic. By presenting real-world case studies from two scientific disciplines, we demonstrate our code’s applicability across domains." "Ultrafast solvent selection with geometric message passing neural networks" "Maarten Dobbelaere, David West, Christian Stevens, Kevin Van Geem" "Exploring the reaction space of flow chemistry" "Maarten Dobbelaere, Lowie Tomme, Christian Stevens, Kevin Van Geem" "Synthesis of 4‐imidoyl‐, 4‐oxiranyl‐ and 4‐propargyloxyphenyl‐substituted β‐lactam building blocks" "Sari Deketelaere, Gurkirat Kaur, Nicola Piens, Daan Deturck, Robin Depestel, Kristof Van Hecke, Christian Stevens, Vipan Kumar, Matthias D'hooghe" "Green mechanochemical synthesis of water-soluble N-sulfonated chitosan" "Casper Van Poucke, Aurèle Vandeputte, Sven Mangelinckx, Christian Stevens" "In the transition towards the use of renewable resources, it is advantageous to be able to use biopolymers that are widely available with desirable functionalities. One of the most promising examples is chitosan. Chitosan can be derived from natural chitin which is cheaply available as a waste product from for example the food industry. However, one major limitation regarding chitosan's biological applicability is its limited solubility in plain water at neutral pH. Generally, to dissolve long-chain chitosan molecules, acidic conditions are required. The most common way to achieve this is by either the direct addition of organic or inorganic acids or via the addition of acidic chitosan salts. However, this severely limits its bioapplications as most biological processes are heavily pH dependent. Herein, we present a green and efficient solventless mechanochemical derivatization method, that involves the solid-state reaction between chitosan and 1,3-propane sultone, to make chitosan plain water soluble, meaning that the macromolecule completely dissolves at neutral pH without acidifying the solution in the process. To our knowledge, this is the most efficient chemical method for plain water-soluble chitosan compared to the current state-of-the-art, requiring a minimal amount of chemical input, as quantified by several green metrics. This could pave the way toward the valorization of waste into new bioactive materials via a sustainable process, taking major steps toward completely closing the loop." "Acidic sophorolipid and antimicrobial peptide based formulation as antimicrobial and antibiofilm agents" "Sahadevan Seena, Rafaela Ferrão, Melike Pala, Sophie Roelants, Wim Soetaert, Christian Stevens, Lino Ferreira, Akhilesh Rai" "Antimicrobial peptides (AMPs) are considered promising candidates to treat various infections in soft tissues and skin. However, no effective treatment based on AMPs has been reached to clinics due to their instability in serum and wounds. Biosurfactants such as acidic sophorolipids (ASLs) of very high concentrations (equal or above 5 mg/mL) have been demonstrated to be antimicrobial agents, however these concentrations might induce cytotoxic effects to human cells. Here, we have demonstrated the synergistic antimicrobial effect of ASL nanoparticles (NPs) and LL37 peptides (below their minimum inhibitory concentrations; MICs) to eradicate Gram-positive and Gram-negative bacteria in human serum (HS) and in the presence of trypsin. The formulations containing ASL NPs (500 mu g/mL) and LL37 peptides (15-25 mu g/mL) effectively kill wide strains of bacteria in 5 % HS and the presence of trypsin. Moreover, the combination of ASL NPs (500 mu g/mL) and LL37 peptides (15 mu g/mL) prevents the formation of S. aureus biofilm and eradicates the one-day old biofilm. Importantly, the combination of ASL NPs and LL37 peptides severely damages the cell membrane of Escherichia coli (E. coli) as shown by atomic force microscopy (AFM). The combination of ASL NPs and LL37 peptides rapidly damages the outer (OM) and inner membrane (IM) of E. coli, while ASL NPs (1000 mu g/mL) alone slowly compromise the integrity of the bacterial membrane. Importantly, the combination of ASL NPs and LL37 peptides is biocompatible to human keratinocyte cells (HaCaTs) and human umbilical vein endothelial cells (HUVECs), and induces the expression of antiinflammatory cytokine in macrophages. Overall, ASL NPs in combination with LL37 peptides might be developed as an effective topical formulation to prevent bacterial infections in the skin."