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Lori Huberman works in the field of fungal genetics, with an emphasis on investigating the genetic mechanisms fungi use to sense and respond to the nutrients and toxins in their environment. In this mSphere of Influence article, she reflects on how "Rapid quantification of mutant fitness in diverse bacteria by sequencing randomly bar-coded transposons" by K. M. Wetmore, M. N. Price, R. J. Waters, J. S. Lamson, et al. (mBio 6:e00306-15, 2015, https://doi.org/10.1128/mBio.00306-15) made an impact on her by establishing technologies that open realistic possibilities for developing high-throughput screening methods to correlate phenotype to genotype in diverse fungal species., Competing Interests: The author declares no conflict of interest.

Organisms must accurately sense and respond to nutrients to survive. In filamentous fungi, accurate nutrient sensing is important in the establishment of fungal colonies and in continued, rapid growth for the exploitation of environmental resources. To ensure efficient nutrient utilization, fungi have evolved a combination of activating and repressing genetic networks to tightly regulate metabolic pathways and distinguish between preferred nutrients, which require minimal energy and resources to utilize, and nonpreferred nutrients, which have more energy-intensive catabolic requirements. Genes necessary for the utilization of nonpreferred carbon sources are activated by transcription factors that respond to the presence of the specific nutrient and repressed by transcription factors that respond to the presence of preferred carbohydrates. Utilization of nonpreferred nitrogen sources generally requires two transcription factors. Pathway-specific transcription factors respond to the presence of a specific nonpreferred nitrogen source, while another transcription factor activates genes in the absence of preferred nitrogen sources. In this review, we discuss the roles of transcription factors and upstream regulatory genes that respond to preferred and nonpreferred carbon and nitrogen sources and their roles in regulating carbon and nitrogen catabolism. KEY POINTS: • Interplay of activating and repressing transcriptional networks regulates catabolism. • Nutrient-specific activating transcriptional pathways provide metabolic specificity. • Repressing regulatory systems differentiate nutrients in mixed nutrient environments., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)