Identification of an itaconic acid degrading pathway in itaconic acid producing Aspergillus terreus
Identification of an itaconic acid degrading pathway in itaconic acid producing Aspergillus terreus
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产衣康酸土曲霉中衣康酸降解途径的鉴定
DOI：
10.1007/s00253-016-7554-0
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发表时间：
2016-09-01
影响因子：
5
通讯作者：
Lu，Xuefeng
中科院分区：
文献类型：
--
作者：
Chen，Mei;Huang，Xuenian;Lu，Xuefeng
衣康酸主要由土曲霉产生，是最具发展前景和灵活性的生物基化学品之一。以前的研究是为了提高衣康酸的产量。通过代谢工程的土地主要集中在其生物合成途径，而衣康酸的降解途径在很大程度上被忽视。在本研究中，我们利用转录组学、蛋白质组学、生物信息学和体外酶学分析方法，确定了衣康酸分解代谢途径中的三个关键酶：衣康酰辅酶A水合酶(ICTA)、衣康酰辅酶A水合酶(ICHA)和柠檬酰辅酶A裂解酶(CCLA)。特鲁斯。在衣康酸分解代谢途径中。以琥珀酰辅酶A为辅基，衣康酸首先被ICTA转化为衣康酰辅酶A，然后衣康酰辅酶A再被ICA水合生成柠檬酰辅酶A。最后，柠檬酰-辅酶A被CCLA裂解为乙酰辅酶A和丙酮酸。此外，ICTA还能催化柠檬酰-辅酶A与琥珀酸反应生成琥珀酸辅酶A和柠檬酸。这些结果首次确定了衣康酸生产过程中衣康酸降解途径中的三个关键酶ICTA、IchA和CCLA。特鲁斯。这些结果将有助于通过代谢工程来改造衣康酸的分解代谢途径，从而提高衣康酸的产量。特鲁斯。
Itaconic acid, one of the most promising and flexible bio-based chemicals, is mainly produced byAspergillus terreus. Previous studies to improve itaconic acid production inA. terreusthrough metabolic engineering were mainly focused on its biosynthesis pathway, while the itaconic acid-degrading pathway has largely been ignored. In this study, we used transcriptomic, proteomic, bioinformatic, and in vitro enzymatic analyses to identify three key enzymes, itaconyl-CoA transferase (IctA), itaconyl-CoA hydratase (IchA), and citramalyl-CoA lyase (CclA), that are involved in the catabolic pathway of itaconic acid inA. terreus. In the itaconic acid catabolic pathway inA. terreus, itaconic acid is first converted by IctA into itaconyl-CoA with succinyl-CoA as the CoA donor, and then itaconyl-CoA is hydrated into citramalyl-CoA by IchA. Finally, citramalyl-CoA is cleaved into acetyl-CoA and pyruvate by CclA. Moreover, IctA can also catalyze the reaction between citramalyl-CoA and succinate to generate succinyl-CoA and citramalate. These results, for the first time, identify the three key enzymes, IctA, IchA, and CclA, involved in the itaconic acid degrading pathway in itaconic acid producingA. terreus. The results will facilitate the improvement of itaconic acid production by metabolically engineering the catabolic pathway of itaconic acid inA. terreus.