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Elife. 2017 Mar 6;6. pii: e22835. doi: 10.7554/eLife.22835.

Novel mechanism of metabolic co-regulation coordinates the biosynthesis of secondary metabolites in Pseudomonas protegens.

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Department of Botany and Plant Pathology, Oregon State University, Corvallis, United States.
Department of Pharmaceutical Sciences, Oregon State University, Corvallis, United States.
US Department of Agriculture, Agricultural Research Service, Horticultural Crops Research Laboratory, Corvallis, United States.


Metabolic co-regulation between biosynthetic pathways for secondary metabolites is common in microbes and can play an important role in microbial interactions. Here, we describe a novel mechanism of metabolic co-regulation in which an intermediate in one pathway is converted into signals that activate a second pathway. Our study focused on the co-regulation of 2,4-diacetylphloroglucinol (DAPG) and pyoluteorin, two antimicrobial metabolites produced by the soil bacterium Pseudomonas protegens. We show that an intermediate in DAPG biosynthesis, phloroglucinol, is transformed by a halogenase encoded in the pyoluteorin gene cluster into mono- and di-chlorinated phloroglucinols. The chlorinated phloroglucinols function as intra- and inter-cellular signals that induce the expression of pyoluteorin biosynthetic genes, pyoluteorin production, and pyoluteorin-mediated inhibition of the plant-pathogenic bacterium Erwinia amylovora. This metabolic co-regulation provides a strategy for P. protegens to optimize the deployment of secondary metabolites with distinct roles in cooperative and competitive microbial interactions.


Pseudomonas protegens; biochemistry; infectious disease; metabolic co-regulation; microbiology; secondary metabolite

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