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Abstract
Organisms inhabit different metabolic states depending on their developmental programming, internal resources, regulatory processes, emergent dynamics (e.g. circadian clocks), and in response to changes in their environments. The Quinic Acid (QA) gene cluster, a model for eukaryotic biochemical networks and their regulation, provides the enzymes and regulatory mechanisms for Neurospora crassa to shift (e.g. from glucose or starvation) to utilization of QA as a sole carbon source. While much of this process is known, the function of qa-x has remained elusive despite the availability of a mutant strain (∆qa-x) for decades. We hypothesized that qa-x either assists in QA flux to central carbon metabolism or exerts broader control over QA metabolism. Continuous in vivo monitoring of metabolism by NMR (CIVM-NMR), a recent approach we developed, revealed latent metabolic phenotypes in the mutant, including net ethanol flux reversal. We demonstrate that this metabolic shift is triggered by quorum sensing in both the mutant and the wild-type, and that the quorum is lower in the qa-x mutant. Homogentisic acid (HGA) accumulation in the mutant indicates a qa-x function downstream of the anabolic QA pathway en route to the TCA cycle and accounts for the one known ∆qa-x phenotype. Finally, initial data indicate that known Saccharomyces cerevisiae quorum sensing signals do not induce the quorum response.