In nature, microbial secondary metabolites are responsible for a myriad of physiological and ecological functions, including microbe-microbe interactions, playing a crucial role in the ecological balance of the microbial world. Cyanobacteria are a diverse and widely distributed group of Gramnegative bacteria capable of oxygenic photosynthesis which are also known to be prolific producers of unique secondary metabolites. In nature, cyanobacteria are usually found in microbial assemblages, as part of phototrophic biofilms, in which different cyanobacteria strains together with members of other bacterial phyla cohabit. Cyanobacteria can produce extracellular polymeric substances (EPS) and polysaccharidic mucilage which creates a favourable microenvironment for microbial communities to grow (also referred to as cyanosphere). Even in laboratorial conditions, cyanobacteria are usually maintained as non-axenic unicyanobacterial cultures, due to the impossibility of growing in axenicity, which highlights the intricate interactions between cyanobacteria and the cyanosphere microbiome. Despite their biotechnological relevance, including the production of clinically important NPs, the bioprospection of cyanobacteria has been mostly restricted to cultivable strains or biofilms from tropical regions, from which large quantities of biomass are possible to harvest. The microbiome composition of the cyanobacteria biofilms on such studies is not a target point, thus, questions on the diversity of cyanobacteria that compose the biofilms across different environments, and which members of other bacteria phyla are concomitantly found are still to be further investigated. Besides, how the biofilm community interact and regulate the production of cyanobacterial NPs is yet to be fully understood. The NPs are produced by biosynthetic gene clusters (BGCs), sets of physically clustered genes that encode the biosynthetic enzymes for a NP pathway. Advances in High Throughput Sequencing (HTS) technologies and “omics” studies have disclosed a large diversity of cyanobacterial BGCs not associated to known NPs. This occurs not only by the disclosure of unknown and uncultivated cyanobacterial diversity and its associated biosynthetic machinery, but also to the existence of cryptic BGCs, and the necessity of triggers to activate silent or downregulated gene clusters, which are usually absent in laboratory cultivation conditions. In cyanobacterial biofilms, we envision that the interaction between the different members of the community might play a preeminent role on the expression of the cyanobacterial BGCs, including secondary metabolites itself.
To address these questions, CYANOBioMe aims to i) conduct a systematic analysis on cyanobacteria-dominated biofilms, across several habitats, to determine its microbiome composition and biosynthetic (active) potential using metagenomics and metatranscriptomics and ii) apply comparative metranscriptomics and metabolomics analysis to cyanobacteria (simulated) biofilms, to infer from species interaction as potential triggers of BGCs expression and metabolites production. To achieve these aims, we propose to explore a holistic understanding of environmental cyanobacterial biolfilms, from microbiome composition to functioning. Interdisciplinary approaches will be integrated, from “omics” strategies targeting the metagenome, metatranscriptome and metabolome of environmental cyanobacterial biofilms to laboratorial co-cultivation studies of unicyanobacterial strains. The cross-disciplinary expertise of the team in microbiology (AR, AV, MC,), chemical ecology (AR, AV, MC) bioinformatics (AR, MC), biosynthesis (MC, SF) and chemistry of natural products (SF) will make possible the integration and understanding of multi-omics data and aid the achievement of the project goals. Overall, CYANOBioMe might open avenues for facilitating the discovery of new NPs, by addressing key culturing interveners and bottlenecks that limit the growth of cyanobacteria in laboratory and identify triggers for cyanobacterial BGCs expression and metabolites production.