Abstract
Genetically encoded small molecules (secondary metabolites) play eminent roles in ecological interactions, as pathogenicity factors and as drug leads. Yet, these chemical mediators often evade detection, and the discovery of novel entities is hampered by low production and high rediscovery rates. These limitations may be addressed by genome mining for biosynthetic gene clusters, thereby unveiling cryptic metabolic potential. The development of sophisticated data mining methods and genetic and analytical tools has enabled the discovery of an impressive array of previously overlooked natural products. This review shows the newest developments in the field, highlighting compound discovery from unconventional sources and microbiomes.
Highlights
Encoded small molecules play eminent roles in ecological interactions, as pathogenicity factors and as drug leads
Eminent examples of genetically programmed molecular assembly lines include the major classes of natural products such as polyketides[4] and nonribosomally synthesized peptides (NRPs)[5], ribosomally synthesized and posttranslationally modified peptides (RiPPs)[6], alkaloids[7], and terpenes[8]
Analyses of genome sequences indicate that the biosynthetic potential of bacteria, fungi, and even higher organisms is much larger than what is observed under laboratory conditions
Summary
Encoded small molecules (secondary metabolites) play eminent roles in ecological interactions, as pathogenicity factors and as drug leads. Linking genes to metabolites and prioritizing cryptic BGCs. Various compounds were discovered by traditional approaches like bioactivity-guided isolation in the past, but the molecular bases of their biosynthesis or congeners with other activity profiles remained unknown. Through a combination of genome mining, imaging mass spectrometry, and expression studies in the natural producer, the BGC was discovered, revealing that siphonazole originates from a mixed polyketide synthase/nonribosomal peptide synthetase (PKS/NRPS) pathway[34].
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