biostudies-literatureUnknownBogdanov ANCCIH NIH HHSNIGMS NIH HHSMicrobial natural products remain an important resource for drug discovery. Yet, commonly employed discovery techniques are plagued by the rediscovery of known compounds, the relatively few microbes that can be cultured, and laboratory growth conditions that do not elicit biosynthetic gene expression among myriad other challenges. Here we introduce a culture independent approach to natural product discovery that we call the Small Molecule In situ Resin Capture (SMIRC) technique. SMIRC exploits in situ environmental conditions to elicit compound production and represents a new approach to access poorly explored chemical space by capturing natural products directly from the environments in which they are produced. In contrast to traditional methods, this compound-first approach can capture sbioRxiv : the preprint server for biology2023.03.02.530684https://www.ebi.ac.uk/biostudies/studies/S-EPMC10312467biostudies-literatureSmall Molecule <i>in situ</i> Resin Capture - A Compound First Approach to Natural Product Discovery.PMC10312467R21 AT010493R01 GM085770Muskat MNLuedtke SJensen PRWu LFBogdanov ASalib MNHammerlindl HAltschuler SJMolinski TFChase ABBarbosa da Silva EO'Donoghue AJfalseSmall Molecule <i>in situ</i> Resin Capture - A Compound First Approach to Natural Product Discovery.Microbial natural products remain an important resource for drug discovery. Yet, commonly employed discovery techniques are plagued by the rediscovery of known compounds, the relatively few microbes that can be cultured, and laboratory growth conditions that do not elicit biosynthetic gene expression among myriad other challenges. Here we introduce a culture independent approach to natural product discovery that we call the Small Molecule In situ Resin Capture (SMIRC) technique. SMIRC exploits in situ environmental conditions to elicit compound production and represents a new approach to access poorly explored chemical space by capturing natural products directly from the environments in which they are produced. In contrast to traditional methods, this compound-first approach can capture s2023-01-01T00:00:00Z2023 May2025-07-09T03:05:16.177Z2025-07-09T03:05:16.177ZS-EPMC103124673739825710.1101/2023.03.02.530684