Large-scale (meta)genomic sequencing of underexplored microbial sources opens up new opportunities for novel NP discovery.

Automated biofoundry workflows are facilitating the refactoring and expression of silent BGCs at scale and speed.

Artificial intelligence has become an important strategy to identify candidate AMPs from complex microbial communities.

The syn-BNP approach opens up new avenues for novel NP discovery in an interdisciplinary and high-throughput manner.

Microbial natural products and their structural analogues have widely used as pharmaceutical agents, especially for infectious diseases and cancer. Despite this success, new structural classes with innovative chemistry and modes of action are urgently needed to be developed to combat the growing antimicrobial resistance and other public health problems. The advances in next-generation sequencing technologies and powerful computational tools open up new opportunities to explore microbial biosynthetic potential from underexplored sources, with millions of secondary metabolites awaiting discovery. The review highlights challenges associated with discovery of new chemical entities, rich reservoirs provided by untapped taxa, ecological niches or host microbiomes, emerging synthetic biotechnologies to unearth the hidden microbial biosynthetic potential for novel drug discovery at scale and speed.

Natural products

Underexplored sources

Biosynthetic potential

Synthetic biology

Artificial intelligence

Antimicrobial peptides

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