Current Status and Future Strategies to Increase Secondary Metabolite Production from Cyanobacteria

Abstract

Cyanobacteria, given their ability to produce various secondary metabolites utilizing solar energy and carbon dioxide, are a potential platform for sustainable production of biochemicals. Until now, conventional metabolic engineering approaches have been applied to various cyanobacterial species for enhanced production of industrially valued compounds, including secondary metabolites and non-natural biochemicals. However, the shortage of understanding of cyanobacterial metabolic and regulatory networks for atmospheric carbon fixation to biochemical production and the lack of available engineering tools limit the potential of cyanobacteria for industrial applications. Recently, to overcome the limitations, synthetic biology tools and systems biology approaches such as genome-scale modeling based on diverse omics data have been applied to cyanobacteria. This review covers the synthetic and systems biology approaches for advanced metabolic engineering of cyanobacteria.

Microbial Secondary Metabolism and Biotechnology

“…Recent research demonstrated that the production of specialized metabolites is mostly coded by clustered genes on chromosomal DNA rather than by plasmidic DNA. However, the related pathways are still not fully clarified and thus provide a new theoretical frontier for academic researchers in enzymology, control and differentiation [4].…”

“…Metabolic engineered-based approaches are now widely applied to cyanobacteria for the industrial production of value-added compounds, including specific metabolites and non-natural biochemicals. However, the review of Jeong et al (2020) [4] covers a large synthetic and systems biology approach for advanced metabolic engineering of cyanobacteria. This involves an overview of known biosynthetic clusters coding for essential compounds, and knowledge of heterologous expression for cyanobacterial secondary metabolite production.…”

Genomics of cyanobacteria: New insights and lessons for shaping our future—A follow-up of volume 65: Genomics of cyanobacteria

“…An important aspect of cyanobacteria is that they produce a wide range of secondary metabolites with diverse chemical structures and biological activities (vitamins, sunscreens, antibiotics, anti-cancer, toxins, etc.) (Cassier-Chauvat, Dive, & Chauvat, 2017;Demay, Bernard, Reinhardt, & Marie, 2019;Jeong et al, 2020;. For instance, at least 800 different secondary metabolites have been identified in marine cyanobacteria so far, a number likely representing a small fraction of the natural product repertoire.…”

“…Cyanobacteria use about 5-6% of their genome length to direct the production of secondary metabolites. For example, it is predicted that the genome of Moorea producens PAL-8-15-08-1 carries 18 NRPS Biosynthetic Gene Clusters ( Jeong et al, 2020). These gene clusters are often large (Cassier-Chauvat et al, 2017;Dittmann et al, 2015;Pearson et al, 2016).…”

“…The synthesis of aeruginosin (a protease inhibitor) is encoded by a 34-kb gene cluster in Planktothrix and Microcystis, while the synthesis of saxitoxin (a neurotoxic alkaloid, which blocks the sodium (Na+) channels in shellfish) is directed by a 25.7 kb gene cluster in Raphidiopsis brookii D9. The corresponding panoply of enzymes (polyketide synthases and non-ribosomal peptide synthases) of interest for synthetic biology can still be increased through gene manipulations with the tools available for the few genetically manipulable strains (Cassier-Chauvat et al, 2017;Jeong et al, 2020). Thus, cyanobacteria, which combine the ability to synthesize a vast array of bioactive molecules with powerful photosynthesis, radiation resistance and effective synthetic biology tools for several model strains, are well suited for future cheap production of a vast array of uniformly 14 C-labeled bioactive compounds, in order to screen for new drugs and analyze their absorption, distribution, metabolism, and excretion properties (Cassier-Chauvat et al, 2017).…”