Polyketides are a remarkable class of natural products with diverse functional and structural diversity. The class includes many medicinally important molecules with antiviral, antimicrobial, antifungal and anticancer properties. Native bacterial, fungal and plant hosts are often difficult to cultivate and coax into producing the desired product. As a result, Escherichia coli has been used for the heterologous production of polyketides, with the production of 6-deoxyerythronolide B (6-dEB) being the first example. Current strategies for production in E. coli require feeding of exogenous propionate as a source for the precursors propionyl-CoA and S-methylmalonyl-CoA. Here, we show that heterologous polyketide production is possible from glucose as the sole carbon source. The heterologous expression of eight genes from the Wood-Werkman cycle found in Propionibacteria, in combination with expression of the 6-dEB synthases DEBS1, DEBS2 and DEBS3 resulted in 6-dEB formation from glucose as the sole carbon source. Our results show that the Wood-Werkman cycle provides the required propionyl-CoA and the extender unit S-methylmalonyl-CoA to produce up to 0.81 mg/L of 6-dEB in a chemically defined media.

中文翻译：

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通过Wood Werkman循环在大肠杆菌中异源产生6-脱氧赤藓醇B。

聚酮化合物是一类非凡的天然产物，具有不同的功能和结构多样性。该类别包括许多具有抗病毒，抗微生物，抗真菌和抗癌特性的重要医学分子。天然细菌，真菌和植物宿主通常很难培养和哄骗产生所需的产品。结果，大肠杆菌已被用于聚酮化合物的异源生产，第一个例子是6-脱氧赤藓醇B（6-dEB）的生产。当前在大肠杆菌中生产的策略要求以外源丙酸酯作为丙酰辅酶A和S的前体来源-甲基丙二酰-CoA。在这里，我们表明异源聚酮化合物可能由葡萄糖作为唯一碳源而产生。在丙酸杆菌中发现了来自伍德-韦克曼循环的八个基因的异源表达，与6-dEB合酶DEBS1，DEBS2和DEBS3的表达相结合，导致了葡萄糖作为唯一碳源形成了6-dEB。我们的结果表明，伍德-韦克曼循环提供了所需的丙酰辅酶A和增量剂S-甲基丙二酰辅酶A，可在化学确定的介质中产生高达0.81 mg / L的6-dEB。