Novel multi-resistant microbial, biofilm and biofouling hybrid isoprenoid inhibitors isolated from MAR4 strains [NI-TECH-2020-28]

Actinomycetes targeted from marine sediments collected off Madeira Archipelago, located at the unexplored Macaronesia Atlantic ecoregion.

Technology Overview

From 413 isolated actinomycetes, phylogenetic characterization based on 16S rRNA gene sequence revealed six strains that were more than 99% similar to the rare MAR4 streptomycete lineage, making this the first report of MAR4 Streptomyces from the Atlantic Ocean. All the 16S rRNA sequences obtained from the six MAR4 strains were deposited on GenBank under the following accession numbers and are already available: 1) PTM-029 (KP869059); 2) PTM-346 (KP869060); 3) PTM-081 (KP869061), PTM-129 (KP869062), PTM-398 (KP869063) and PTM-420 (KP869064).

The MAR4 Streptomyces lineage was first recognized as part of a survey of cultured marine actinobacteria and has been identified as a prolific source of hybrid isoprenoids (HI) with a mixed biosynthetic origin including an isoprene-derived moiety. Terpenoids are commonly obtained from several natural product sources, such as plants, insects, fungi and marine invertebrates like soft corals, but very rarely from bacteria. HI classes described in MAR4 strains comprise napyradiomycins, marinones, lavanducyanins, nitropyrrolin, and prenylated phenazines. These actinomycete-derived HI compounds exhibit potent biological activities, such as antibiotic and anticancer, e.g. the commercially important aminocoumarin antibiotics.

Large scale fermentation of the Madeira MAR4 strains led to the isolation of several new napyradiomycin derivative natural products. Herein we intent to patent the isolation, structure elucidation by comprehensive spectroscopic analysis and by X-ray crystallography, and antimicrobial, biofilm and biofouling activities of these new compounds.

New hybrid isoprenoids with antibacterial, anti-biofilm and anti-fouling activity have been characterized. These may be incorporated and used in developing new products in a wide range of applications and markets. Namely, antibiotic resistance, clinical biofilms and marine fouling are major worldwide health, social and environmental problems, leading to economic burdens worldwide. To meet these challenges, we focused our research efforts in obtaining marine bio-based products with inhibition properties against bacterial human and veterinary pathogens, as well as the inhibition of fouling organisms to be used as added value products in industry. Among others, paints and coatings for surfaces submerged in water and in the health care and well-being industry.

The new inhibitors will benefit various industries, addressing the enormous threat that bacterial infections and drug resistance pose to humanity and, and addressing environmental issues related to the lack of available environmentally friendly anti-fouling products. Prophylactic / therapeutic solutions will benefit SMEs and increase the sustainability of health systems and care, through improved productivity resulting from reducing the number of surgical interventions, premature death and costly medical interventions. Identifying new alternative sources of renewable raw materials will benefit environmental habitats, relieving pressure on natural resources.

Stage of Development

TRL4 – Validated in laboratorial environment.

Intellectual Property

PT115055

Know-how based.

NOVA Inventors

Susana Gaudêncio

Rita Gonçalves Almeida

Maria Florbela Pereira

Ilda Sanches