Biosynthetic potential of the global ocean microbiome

Area of Science:

• Microbiology
• Metagenomics
• Biochemistry

Background:

• Natural microbial communities exhibit vast phylogenetic and metabolic diversity, holding potential for discovering novel enzymes and compounds.
• Studying microbial diversity to identify biosynthetic pathways and their hosts is challenging, especially in underexplored environments like the open ocean.
• The biosynthetic potential of marine microorganisms remains largely uncharacterized due to limitations in large-scale genome-resolved data analysis.

Purpose of the Study:

• To investigate the diversity and novelty of biosynthetic gene clusters in the global ocean.
• To identify previously unknown enzymes and natural products from underexplored microbial groups.
• To characterize novel biosynthetic pathways and their associated bioactive compounds.

Main Methods:

• Integration of approximately 10,000 microbial genomes from cultivated and single-cell sources.
• Reconstruction of over 25,000 draft genomes from more than 1,000 seawater samples.
• Analysis of genome-resolved data to identify and characterize biosynthetic gene clusters.

Main Results:

• Discovery of approximately 40,000 putative, mostly novel, biosynthetic gene clusters.
• Identification of numerous gene clusters within unexpected phylogenetic groups, including the uncultivated bacterial lineage 'Candidatus Eudoremicrobiaceae'.
• Characterization of phospeptin and pythonamide pathways, revealing unusual compound structures and enzymology.

Conclusions:

• Microbiomics-driven strategies are effective for exploring undescribed enzymes and natural products in underexplored microbial communities.
• The ocean harbors a rich, largely untapped reservoir of microbial biosynthetic diversity.
• This research expands the known landscape of microbial natural products and their biosynthetic pathways.