Prenylated aromatic compounds are important intermediates in the biosynthesis of bioactive molecules such as 3-chromanols from plants, ubiquinones from prokaryotes and meroterpenoids from sponges. Biosynthesis of prenylated aromatic compounds using prokaryotic microorganisms has attracted increasing attention in the field of synthetic biology. In this study, we demonstrated that the production of 3-geranyl-4-hydroxybenzoic acid (GBA) and a variety of GBA analogues was feasible in a metabolically engineered E. coli by using XimB, a special prenyltransferase involved in the biosynthesis of xiamenmycin A in Streptomyces xiamenensis 318. XimB exhibits broad substrate specificity and can catalyze the transfer reaction of prenyl moieties with different carbon chain lengths to both the natural substrate 4-hydroxybenzoate (4-HBA) and to different substituted 4-HBA derivatives at C-2 and C-3. Feeding 4-HBA to an engineered E. coli equipped with a hybrid mevalonate pathway increased the production of GBA up to 94.30 mg/L. Considerable amounts of other GBA derivatives, compounds 4, 5, 6, 7, and 9, can be achieved by feeding precursors. The plug-and-play design for inserting C₅, C₁₅, and C₂₀ prenyl diphosphate synthetases under the control of the T7 promoter resulted in targeted production of 3-dimethylallyl, 3-farnesyl-, and 3-geranylgeranyl-4-hydroxybenzoic acid, respectively. Furthermore, the valuable benzopyran xiamenmycin B was successfully produced in E. coli R7-MVA by coexpression of a complete biosynthetic gene cluster, which contains ximBDE.

中文翻译：

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在工程化大肠杆菌中过表达底物混杂异戊二烯基转移酶XimB来合成炔丙基4-羟基苯甲酸酯衍生物的生物合成。

烯丙基化的芳族化合物是生物活性分子（例如植物的3-chromanol），原核生物的泛醌和海绵的类萜的生物合成中的重要中间体。使用原核微生物生物合成烯丙基化的芳族化合物已经在合成生物学领域引起了越来越多的关注。在这项研究中，我们证明了通过使用XimB（一种参与厦门生物素A生物合成的特殊异戊二烯基转移酶），在代谢工程化的大肠杆菌中生产3-香叶基-4-羟基苯甲酸（GBA）和多种GBA类似物是可行的。在链霉菌xiamenensis318. XimB具有广泛的底物特异性，并且可以催化具有不同碳链长度的异戊二烯基部分转移至天然底物4-羟基苯甲酸酯（4-HBA）以及C-2和C-3上不同的取代的4-HBA衍生物。将4-HBA喂入装有杂合甲羟戊酸途径的工程化大肠杆菌中，可使GBA的产量增加至94.30 mg / L。相当大的量的其它GBA衍生物，化合物4，5，6，7，和9，可以通过进料前体来实现的。用于插入C ₅，C ₁₅和C ₂₀的即插即用设计在T7启动子的控制下，异戊二烯基二磷酸异戊二烯合成酶分别导致3-二甲基烯丙基，3-法呢基-和3-香叶基香叶基-4-羟基苯甲酸的靶向生产。此外，有价值的苯并吡喃xiamenmycin乙成功中制备大肠杆菌R7-MVA通过一个完整的生物合成基因簇，其含有共表达ximBDE。