Acceso a fuentes novedosas de productos naturales: Alcance multiómico innovador y transdisciplinar para el descubrimiento de metabolitos bioactivos en Actinobacterias y Cianobacterias de ambientes extremos

Bacteria have been recognized as one of the major sources of natural products in drug
development. However, the discovery of novel microbial bioactive metabolites is becoming difficult
because some bioactive compounds are being more frequently re-discovered. Thus, since most of
the currently used antibiotics and antineoplastic drugs have been isolated from microorganisms is
that metabolites re-discovery is not only a microbial prospection bottleneck, but it is a limitation on
science contribution to current prior global health issues such as antibiotic-resistance and
chemotherapy-resistant cancer. Nevertheless, most of the metabolic diversity of some groups of
microorganisms has not yet been revealed and they still being a promising source of valuable novel
metabolites. Multiple approaches for drug discovery have been proposed to overcome this issue,
however truly novel molecular diversity of natural product sources is still needed. Bacterial groups
such as rare Actinobacteria and Cyanobacteria have been suggested as an untapped source to
search for important novel bioactive metabolites, particularly, those inhabiting extreme
environments. It has been reported that these groups of bacteria can harbor a great number of
biosynthetic gene clusters (BGCs) to produce multiple secondary metabolites with potential
biological activities, nonetheless, most of the BGCs are cryptic or remains silent under traditional
culture conditions. In this proposal, we hypothesize that silent novel metabolites from untapped rare
Actinobacteria and Cyanobacteria can be activated by accurate elicitation stimuli and genetic knockdown of basal metabolic pathways, which will be a suitable approach for potential drug development
against current drug-resistant major health threats (i.e. multidrug resistant bacteria and
chemotherapy-resistant cancer).The aim of this project is to boost the production of novel bioactive
molecules in microorganisms adapted to survive the extreme environments (i.e. rare Actinobacteria
and Cyanobacteria), by the application of an innovative multi-omics and genetic engineering
approach for prioritization and activation of the silent metabolic pathways. This proposal will provide
us a robust validation opportunity to boosts the potential candidate genes and metabolic pathways
for increasing bioactive molecules production of untapped extreme bacteria avoiding the
rediscovery of natural products. Therefore, we will be able to obtain completely new metabolites
with bioactivity against current health threats. Moreover, our proposed approach will create a
paradigm for future programs on microbial drug discovery.

Impulsar la producción de nuevas moléculas bioactivas en microorganismos
adaptados a sobrevivir en ambientes extremos (Actinobacterias y Cianobacterias), mediante la
aplicación de un innovador enfoque de ingeniería genética y multiómica para la priorización y
activación de las vías metabólicas silenciosas.

Aplicaciones Biomédicas y Biotecnología Ambiental