Itaconic acid production is regulated by LaeA in Aspergillus pseudoterreus

• Published in: Metabolic engineering communications Vol. 15; p. e00203
• Main Authors: Pomraning, Kyle R., Dai, Ziyu, Munoz, Nathalie, Kim, Young-Mo, Gao, Yuqian, Deng, Shuang, Lemmon, Teresa, Swita, Marie S., Zucker, Jeremy D., Kim, Joonhoon, Mondo, Stephen J., Panisko, Ellen, Burnet, Meagan C., Webb-Robertson, Bobbie-Jo M., Hofstad, Beth, Baker, Scott E., Burnum-Johnson, Kristin E., Magnuson, Jon K.
• Format: Journal Article
• Language: English
• Published: United States Elsevier B.V 01.12.2022; Elsevier
• Subjects: Aspergillus; Aspergillus pseudoterreus; BASIC BIOLOGICAL SCIENCES; biochemical pathways; biomass; biosynthesis; feedstocks; Full Length; Itaconic acid; laeA; metabolome; Multi-omics; multigene family; Phosphate; phosphates; Process robustness; proteome; secondary metabolites; sugars; transcriptome; Itaconic acid; laeA; Aspergillus pseudoterreus; Process robustness; Phosphate; Multi-omics
• ISSN: 2214-0301; 2214-0301
• DOI: 10.1016/j.mec.2022.e00203

The global regulator LaeA controls secondary metabolism in diverse Aspergillus species. Here we explored its role in regulation of itaconic acid production in Aspergillus pseudoterreus. To understand its role in regulating metabolism, we deleted and overexpressed laeA, and assessed the transcriptome, proteome, and secreted metabolome prior to and during initiation of phosphate limitation induced itaconic acid production. We found that secondary metabolite clusters, including the itaconic acid biosynthetic gene cluster, are regulated by laeA and that laeA is required for high yield production of itaconic acid. Overexpression of LaeA improves itaconic acid yield at the expense of biomass by increasing the expression of key biosynthetic pathway enzymes and attenuating the expression of genes involved in phosphate acquisition and scavenging. Increased yield was observed in optimized conditions as well as conditions containing excess nutrients that may be present in inexpensive sugar containing feedstocks such as excess phosphate or complex nutrient sources. This suggests that global regulators of metabolism may be useful targets for engineering metabolic flux that is robust to environmental heterogeneity. •The Itaconic acid biosynthetic gene cluster is regulated by laeA.•LaeA is required for production of itaconic acid.•Overexpression of laeA attenuates genes involved in phosphate acquisition.•Global regulator engineering increases robustness of itaconic acid production.