Servizio Comunitario di Informazione in materia di Ricerca e Sviluppo - CORDIS

Periodic Report Summary 1 - MICROSMETICS (Exploitation of microbial biodiversity for the discovery and development of novel cosmeceutical agents)

The aim of MICROSMETICS project is to discover and carry to the stage of development innovative products in the area of cosmeceuticals originating from global biodiversity using emerging and state of the art technologies in the field of biotechnology, natural products chemistry and applied microbiology. More specifically, MICROSMETICS scientific concept involves the discovery of novel natural products originating from global microbial biodiversity. Already existing culture collections of fungi and actinomycetes will be exploited incorporating modern high throughput platforms (in silico & in vitro) for the rational and targeted selection of the most promising strains. Advanced analytical approaches and techniques will be applied for the efficient, accelerated and advantageous isolation and identification of natural constituents as well as the quality assessment of the lead products. A broad spectrum of bioassays will be incorporated for the evaluation of anti-ageing, more specifically anti-oxidant, skin-protecting, and skin-whitening activity of all derived products. Attention will be given to the selection and optimisation of fermentation technologies used at pilot scale for the production of new active raw materials to be used in the cosmetic industry.

In order to achieve those goals, as a first step a Rational Drug Design approach has been developed. Starting from the CosIng Repository of the European Commission, an accurate functional prediction model was created for all known cosmetic functions. Additionally it was constructed the homology models of specific cosmetic target receptors (tyrosinase, elastase, hyaluronidase and collagenase) for which the appropriate in vitro tests have already been developed. More than 40.000 known microbial metabolites were processed through a consensus scoring prediction protocol using: a) functional prediction model b) virtual screening procedure for the above 4 selected receptors c) similarity search based on all known molecules from literature that bind to the specific receptors and d) toxicological profile filtering. Combining all the results with functional prediction model and toxilological profile filtering, 110 microorgnanisms were selected that can produce those metabolites or analogues.

Among them 54 fungi and 56 actinomycetes from the global biodiversity (including strains from Antarctica, Alaska, Spain, New Caledonia, Hawaii, South Africa, Comoros Island etc) were cultivated under “nutritional arrays” (different culture conditions) in order each single strain to produce ten different extracts and thus exploit all the potential chemodiversity that microorganisms can produce. In total 1082 sample extracts (614 actinomycetous extracts & 425 fungal extracts) have been generated, then were filtered and prepared in 96 barcoded well format and were shipped for high throughput screening.

A broad spectrum of bioassays have being incorporated for the evaluation of anti-ageing, more specifically anti-oxidant, skin-protecting, and skin-whitening activity of all derived products. For the evaluation of the 1082 extracts concerning the antioxidant activity the DPPH and ABTS assays were used. Skin-protecting was evaluated by measuring spectrophotometrically the inhibitory properties of samples against enzymes which are related to the elasticity and moisture of the skin (elastase, collagenase, and caseinase). The skin whitening activities were determined by the tyrosinase assay, using L-DOPA as substrate. Finally for the safety of those extracts cytotoxicity was evaluated on A2058, CCD25sk, HepG2 cell lines by the MTT method. The results of the above bioassays permitted the elimination of all toxic and non active extracts.

Among the 1082 extracts the top 100 were selected for metabolomics analysis and a strategy combining UHPLC/Orbitrap-HRMS, in positive and negative modes, with multivariate statistical methods was applied. All derived chromatograms have been analyzed and a positive correlation between the profiles of the extracts with the aforementioned bioassays was observed. Thus, through this metabolomics analysis the 20 most promising extracts (19 strains under 14 conditions) that represent the clusters have been forwarded for large-scale cultivation and for confirmation of the activity. In total 8 fungi and 12 actinomycetes were selected for further investigation.

All strains were cultivated with the optimum media for producing the active metabolites in a 1 L scale fermentation. Among them some confirmed the activity while in others the large scale cultivation failed to produce the same activity and metabolites and thus their cultivation is currently re-evaluated. For those extracts that confirmed their activity a full analysis of their bioactive metabolites is underway.

The work that has been performed so far has been implemented by both seconded and recruited researcher. In total 37.5 person months of exchanges have taken place between industry and academia and 36 months of recruitments. Overall MICROSMETICS aspires to comprise a successful model of an efficient, long-lasting collaboration between Industry and Academia.

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Life Sciences