VAlorization of secondary bacterial Metabolites in AGronomy and PHARmaceutical – VAMAGPHAR

In the agronomy, the increasing number of reports in the field of plant-bacteria-fungi interactions provides more and more knowledge concerning the nature and function of the microbial communities of the rhizosphere (the microbiome). These plant-microorganisms interactions can be, for a large part, linked to microbial secondary metabolites secreted by these microorganisms, but numerous ones are not yet characterized.
Studies of the direct use of bacteria in agronomic formulations will not be targeted by this study, it is the secondary metabolites by particular bacteria that will be our focus. The following reasons have guided this choice:
- (i) An environmental and societal need prompts us to produce pesticide-free food and the increased market demand for greater quantities of food.
- (ii) The bacteria selected in this study showed an effective agronomic effect to stimulate the plants and were not studied for the applications envisaged in this project.
- (iii) Replacing existing agronomic formulations by products based on the secondary metabolites responsible for activities with improved efficiency while respecting the environment.
- (iv) The chemical variety of the secondary metabolites produced by these bacteria prompts us to evaluate them for pharmaceutical activities (example resistance cases). This task can provide a major opening to future pharmaceutical development projects.
The production of secondary metabolites from bacteria (Agronutrition) and extraction, fractionation and identification of molecules (LGC-pharma) have already been performed on two models bacteria (Burkholderia sp. and Bacillus megaterium) as part of a collaborative thesis (Belkacem MA, 2016). The work was focused on low volatile extracts followed by the identification by GC-HRMS. One hundred molecules have been identified and twenty of them have been cited in the literature for the first time. This early original results have encouraged us to expand the work with other partners, with other goals and other microorganisms. Pharmaceutical activities (antioxidant, antimicrobial and cytotoxic) were chosen following interesting activities obtained during the thesis work of M Belkacem MA.
The objective of VAMAGPHAR is to identify and develop secondary bacterial metabolites that can be used in agriculture as Biostimulants and/or pharmaceutical treatment as a new source of biologically active molecules, to answer questions of public health indirectly (agriculture) by substituting the input of chemical fertilizers and pesticides or directly (pharmaceutical). This requires a large interdisciplinary cooperation between different specialists (collaboration with private companies): agronomists, microbiologists, chemists and biochemists to obtain the innovative products.
The overall initial methodology proposed in the VAMAGPHAR project to achieve these objectives includes the following key steps:
(i) production of secondary metabolites from soil bacteria, they are effective for the growth of plants and not studied (Streptomyces beta-vulgaris, Burkholderia sp., Pseudomonas putida, Paenibacillus sp, Ochrobactrum sp., Enterobacter ludwigii and Bacillus mucilaginosus).
(ii) optimization and identification of chemical composition of volatile compounds (on-line and by trapping on adsorbing phase),
(iii) extraction, evaluation of the agronomic and pharmaceutical activities and bioguided fractionation of interesting extracts to isolate the active substances.
(iv) process optimization production of the extracts and/or active molecules,
(v) develop formulations from active molecule or extract in the agronomic and in vivo fields for the pharmaceutical (preliminary) activities.
A multidisciplinary research consortium gathering analytical chemistry (LGC-pharma), identification of volatiles compounds (ISA), production process of secondary bacterial metabolites (LGC-process) and 2 companies (Agronutrition & Explorair) was thus built.