Itaconic acid production is regulated by LaeA in Aspergillus pseudoterreus

IF 3.7 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Kyle R. Pomraning , Ziyu Dai , Nathalie Munoz , Young-Mo Kim , Yuqian Gao , Shuang Deng , Teresa Lemmon , Marie S. Swita , Jeremy D. Zucker , Joonhoon Kim , Stephen J. Mondo , Ellen Panisko , Meagan C. Burnet , Bobbie-Jo M. Webb-Robertson , Beth Hofstad , Scott E. Baker , Kristin E. Burnum-Johnson , Jon K. Magnuson , for the Agile BioFoundry
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引用次数: 7

Abstract

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.

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假地曲霉衣康酸的产生受LaeA调控
全球调节剂LaeA控制着多种曲霉种的次级代谢。本文探讨了其在假地曲霉衣康酸生产调控中的作用。为了了解其在调节代谢中的作用,我们删除和过表达laeA,并在磷酸盐限制诱导衣康酸产生之前和开始期间评估转录组、蛋白质组和分泌代谢组。我们发现二级代谢产物簇,包括衣康酸生物合成基因簇,受laeA调控,laeA是衣康酸高产生产所必需的。LaeA的过表达增加了关键生物合成途径酶的表达,减弱了参与磷酸盐获取和清除的基因的表达,从而以牺牲生物量为代价提高衣康酸的产量。在优化条件下,以及在含有过量磷酸盐或复杂营养源等廉价糖原料中可能存在的过量营养条件下,观察到产量增加。这表明,代谢的全局调节因子可能是工程代谢通量的有用靶点,对环境异质性具有鲁棒性。
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来源期刊
Metabolic Engineering Communications
Metabolic Engineering Communications Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
13.30
自引率
1.90%
发文量
22
审稿时长
18 weeks
期刊介绍: Metabolic Engineering Communications, a companion title to Metabolic Engineering (MBE), is devoted to publishing original research in the areas of metabolic engineering, synthetic biology, computational biology and systems biology for problems related to metabolism and the engineering of metabolism for the production of fuels, chemicals, and pharmaceuticals. The journal will carry articles on the design, construction, and analysis of biological systems ranging from pathway components to biological complexes and genomes (including genomic, analytical and bioinformatics methods) in suitable host cells to allow them to produce novel compounds of industrial and medical interest. Demonstrations of regulatory designs and synthetic circuits that alter the performance of biochemical pathways and cellular processes will also be presented. Metabolic Engineering Communications complements MBE by publishing articles that are either shorter than those published in the full journal, or which describe key elements of larger metabolic engineering efforts.
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