Exploiting a Global Regulator for Small Molecule Discovery in <i>Photorhabdus luminescens</i> Renee Kontnik Jason M. Crawford Jon Clardy 10.1021/cb100117k.s001 https://acs.figshare.com/articles/journal_contribution/Exploiting_a_Global_Regulator_for_Small_Molecule_Discovery_in_i_Photorhabdus_luminescens_i_/2751730 Bacterially produced small molecules demonstrate a remarkable range of structural and functional diversity and include some of our most useful biological probes and therapeutic agents. Annotations of bacterial genomes reveal a large gap between the number of known small molecules and the number of biosynthetic genes/loci that could produce such small molecules, a gap that most likely originates from tight regulatory control by the producing organism. This study coupled a global transcriptional regulator, HexA, to secondary metabolite production in <i>Photorhabdus luminescens,</i> a member of the Gammaproteobacteria that participates in a complex symbiosis with nematode worms and insect larvae. HexA is a LysR-type transcriptional repressor, and knocking it out to create a <i>P. luminescens</i> Δ<i>hexA</i> mutant led to dramatic upregulation of biosynthesized small molecules. Use of this mutant expanded a family of stilbene-derived small molecules, which were known to play important roles in the symbiosis, from three members to at least nine members. 2010-07-16 00:00:00 Photorhabdus luminescensBacterially Photorhabdus luminescens HexA transcriptional regulator member insect larvae luminescens Δ hexA Global Regulator metabolite production molecule Small Molecule Discovery gap symbiosi nematode worms