Biosynthesis of bioactive O-methylated flavonoids in Escherichia coli
Biosynthesis of bioactive O-methylated flavonoids in Escherichia coli
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DOI：
10.1007/s00253-013-5020-9
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发表时间：
2013-08-01
影响因子：
5
通讯作者：
Ahn, Joong-Hoon
中科院分区：
文献类型：
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作者：
Kim, Min-Ji;Kim, Bong-Gyu;Ahn, Joong-Hoon
在大肠杆菌中合成了两种具有生物活性的o -甲基黄酮类化合物，sakururetin （7- o -甲基柚皮素）和ponciretin （7- o -甲基柚皮素）。樱素抑制稻瘟病病菌的萌发，而ponciretin是一种潜在的幽门螺杆菌抑制剂。为此，我们重建了柚皮素在大肠杆菌中的生物合成途径。首先，在大肠杆菌中设计了导致酪氨酸生物合成的莽草酸途径，以增加可用酪氨酸的数量。其次，酪氨酸解氨酶（TAL）、4-香豆油酰基辅酶a连接酶（4CL）、查尔酮合成酶（CHS）和o -甲基转移酶（OMT）等与红皮素和樱花素的生物合成有关的基因过度表达。为了增加辅酶A （CoA）的供应，删除了一个基因（icdA，异柠檬酸脱氢酶）。在大肠杆菌中以葡萄糖为原料，分别以42.5 mg/L和40.1 mg/L的浓度合成了ponciretin和sakururetin。
Two bioactive O-methylflavonoids, sakuranetin (7-O-methylnaringenin) and ponciretin (7-O-methylnaringenin), were synthesized in Escherichia coli. Sakuranetin inhibits germination of Magnaporthe grisea, and ponciretin is a potential inhibitor of Helicobacter pylori. To achieve this, we reconstructed the naringenin biosynthesis pathway in E. coli. First, the shikimic acid pathway, which leads to the biosynthesis of tyrosine, was engineered in E. coli to increase the amount of available tyrosine. Second, several genes for the biosynthesis of ponciretin and sakuranetin such as tyrosine ammonia lyase (TAL), 4-coumaroyl CoA ligase (4CL), chalcone synthase (CHS), and O-methyltransferase (OMT) were overexpressed. In order to increase the supply the Coenzyme A (CoA), one gene (icdA, isocitrate dehydrogenase) was deleted. Using these strategies, we synthesized ponciretin and sakuranetin from glucose in E. coli at the concentration of 42.5 mg/L and 40.1 mg/L, respectively.