Metabolic engineering of Saccharomyces cerevisiae for de novo production of dihydrochalcones with known antioxidant, antidiabetic, and sweet tasting properties.
Metabolic engineering of Saccharomyces cerevisiae for de novo production of dihydrochalcones with known antioxidant, antidiabetic, and sweet tasting properties.
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酿酒酵母的酿酒酵母的代谢工程从从头生产二氢切尔科酮，具有已知的抗氧化剂，抗糖尿病和甜味特性。
DOI：
10.1016/j.ymben.2016.10.019
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发表时间：
2017-01
影响因子：
8.4
通讯作者：
Naesby M
中科院分区：
文献类型：
--
作者：
Eichenberger M;Lehka BJ;Folly C;Fischer D;Martens S;Simón E;Naesby M
二氢查耳酮是植物次级代谢物，其包含作为抗氧化剂、抗糖尿病剂或甜味剂具有重要商业价值的分子。迄今为止，它们在微生物中的异源生物合成仅通过前体进料或作为工程化用于类黄酮生产的菌株中的次要副产物来实现。在此，在酿酒酵母中过表达天然ScTSC 13以增加其将对香豆酰-CoA还原为对二氢香豆酰-CoA的副活性。根皮素，第一个承诺的二氢查耳酮，从头生产，实现了额外的相关途径酶的共表达。柚皮素，一个主要的副产品的初始途径，几乎消除了使用查耳酮合酶从大麦与意想不到的底物特异性。通过进一步延伸从根皮素的途径与装饰酶具有已知的特异性的二氢查耳酮，并通过利用底物的灵活性参与类黄酮的生物合成，从头生产的抗氧化剂分子nothofagin，抗糖尿病分子根皮苷，甜分子柚皮苷二氢查耳酮，和3-羟基根皮素实现。根皮素在S.啤酒。从头途径延伸到各种商业利益的二氢查耳酮。大麦CHS对根皮素的产生表现出非常高的特异性。
Dihydrochalcones are plant secondary metabolites comprising molecules of significant commercial interest as antioxidants, antidiabetics, or sweeteners. To date, their heterologous biosynthesis in microorganisms has been achieved only by precursor feeding or as minor by-products in strains engineered for flavonoid production. Here, the native ScTSC13 was overexpressed in Saccharomyces cerevisiae to increase its side activity in reducing p-coumaroyl-CoA to p-dihydrocoumaroyl-CoA. De novo production of phloretin, the first committed dihydrochalcone, was achieved by co-expression of additional relevant pathway enzymes. Naringenin, a major by-product of the initial pathway, was practically eliminated by using a chalcone synthase from barley with unexpected substrate specificity. By further extension of the pathway from phloretin with decorating enzymes with known specificities for dihydrochalcones, and by exploiting substrate flexibility of enzymes involved in flavonoid biosynthesis, de novo production of the antioxidant molecule nothofagin, the antidiabetic molecule phlorizin, the sweet molecule naringin dihydrochalcone, and 3-hydroxyphloretin was achieved. De novo biosynthesis of phloretin in S. cerevisiae. De novo pathway extended to various dihydrochalcones of commercial interest. A barley CHS exhibits very high specificity for phloretin production.