Blue Light-Dependent Pre-mRNA Splicing Controls Pigment Biosynthesis in the Mushroom .

Light induces the production of ink-blue pentacyclic natural products, the corticin pigments, in the cobalt crust mushroom Terana caerulea. Here, we describe the genetic locus for corticin biosynthesis and provide evidence for a light-dependent dual transcriptional/cotranscriptional regulatory mechanism. Light selectively induces the expression of the gene encoding the gateway enzyme, the first described mushroom polyporic acid synthetase CorA, while other biosynthetic genes for modifying enzymes necessary to complete corticin assembly are induced only at lower levels. The strongest induction was observed following exposure to blue and UV light. A second layer of regulation is provided by the light-dependent splicing of the three introns in the pre-mRNA of . Our results provide insight into the fundamental organization of how mushrooms regulate natural product biosynthesis. The regulation of natural product biosyntheses in mushrooms in response to environmental cues is poorly understood. We addressed this knowledge gap and chose the cobalt crust mushroom as our model. Our work discovered a dual-level regulatory mechanism that connects light as an abiotic stimulus with a physiological response, i.e., the production of dark-blue pigments. Exposure to blue light elicits strongly increased transcription of the gene encoding the gateway enzyme, the polyporic acid synthetase CorA, that catalyzes the formation of the pigment core structure. Additionally, light is a prerequisite for the full splicing of pre-mRNA and, thus, its proper maturation. Dual transcriptional/cotranscriptional light-dependent control of fungal natural product biosynthesis has previously been unknown. As it allows the tight control of a key metabolic step, it may be a much more prevalent mechanism among these organisms.