Plant (Bio)Actives

Plant secondary metabolism is rich in compounds (i.e. phytochemicals) with promising (bio)activities or functionalities. These (bio)active phytochemicals can be utilized for the benefit of human, animal and plant health. For instance, the rich stereochemical and functional group diversity of phytochemicals offers a wide range of functionalities, including the inhibition of unwanted microorganisms and the development of novel alternatives to traditional antimicrobials.

The Plant (Bio)Actives group focusses on promising antimicrobial phytochemicals. To obtain these antimicrobials, we employ two main strategies: inducing production in-planta using diverse (a)biotic elicitors and valorizing from agri-food by-products.

Description of theme

The work of the Plant (Bio)Actives group lies at the intersection of (phyto)chemistry, microbiology and (in-silico) molecular modelling. More specifically, our aim is to (i) characterize the antimicrobial properties of phytochemicals; (ii) predict and rationalize their (quantitative) structure-activity relationships (QSAR); and (iii) elucidate their mode of action (MoA) and explore synergistic combinations. At Plant (Bio)Actives, in-silico modelling is integrated with in-vitro evidence to rationalize and predict the properties and MoA of antimicrobial phytochemicals.

1) Antimicrobial properties and synergistic combinations

Phytochemicals have demonstrated effectiveness as antimicrobials against bacteria (cells and spores), fungi and viruses. An interesting strategy to control microorganisms is to design multi-targeted antimicrobial combinations, mimicking how plants respond to pathogens. To develop effective synergistic combinations, it is essential to first characterize the different functionalities of different families of phytochemicals (e.g. inhibition of specific proteins, bacterial membrane disruption, efflux pump inhibition, oxidative stress induction). Quantifying their activity and mapping their spectrum of activity are critical aspects of this research. By using synergistic combinations of plant antimicrobials (i) the potency of the antimicrobial cocktail is enhanced; (ii) dosages can be reduced, making this approach more feasible for applications such as food preservation; and (iii) the risk of persistent or resistant cell survival is significantly minimized.

2) Structure-activity relationships (SAR)

The activity of phytochemicals is strongly linked to their structure. Rather subtle structural differences can lead to a substantial change in the antimicrobial activity. Quantitative SAR analysis is a chemometric tool that enables (i) predictive assessment for an efficient discovery and isolation of antimicrobial phytochemicals (e.g. reducing the number of purification experiments); (ii) accelerated design and optimization of lead antimicrobial scaffolds; and (iii) insights into the molecular properties critical for activity. A balanced approach that combines predictive assessment and in-vitro screening is essential to guide this research effectively.

3) Mode of action

To apply plant-derived antimicrobials in areas such as food, feed or environment, their molecular mechanisms should be well-defined and validated. The elucidation of the molecular targets of antimicrobial phytochemicals include in-vitro assays and in-silico tools. In-vitro assays include cell-based (fluorescence) assays, MS-based targeted analysis, and -omics profiling. In-silico tools include the calculation of molecular properties, 3D pharmacophore modelling, molecular docking and MD simulations. Strong collaborations with other fundamental research groups enable a comprehensive understanding of the mode of action.

Research Projects