The biosynthesis of natural products often requires eukaryotic cytochrome P450s (P450s) in combination with P450 reductase, in physical proximity, to perform electron-transfer reactions. Unfortunately, functional expression of eukaryotic P450s in bacteria remains generally difficult. Here we report an electron channelling strategy based on the application of Photorhabdus luminescens CipB scaffold protein, which allows efficient electron transfer between P450s and reductases by bringing these enzymes in close proximity. The general applicability of this electron channelling strategy is proved by developing recombinant Escherichia coli strains producing lutein, (+)-nootkatone, apigenin and l-3,4-dihydroxyphenylalanine (l-DOPA), each of which requires P450s in its biosynthetic pathway. The production titres are then further enhanced by increasing the haem pathway flux or by optimization of the culture conditions. Remarkably, the final lutein strain produced 218.0 mg l⁻¹ of lutein with a productivity of 5.01 mg l⁻¹ h⁻¹ in fed-batch fermentation under optimized culture conditions.

天然产物的生物合成通常需要真核细胞色素 P450 (P450) 与 P450 还原酶在物理上接近，以进行电子转移反应。不幸的是，真核生物 P450 在细菌中的功能表达通常仍然很困难。在这里，我们报告了一种基于Photorhabdus luminescens CipB 支架蛋白应用的电子通道策略，该策略通过使 P450 和还原酶之间的有效电子转移使这些酶靠近。这种电子通道策略的普遍适用性通过开发生产叶黄素、(+)-nootkatone、芹菜素和l -3,4-二羟基苯丙氨酸的重组大肠杆菌菌株得到证明。-DOPA），其中每一种都需要在其生物合成途径中使用 P450。然后通过增加血红素通路通量或通过优化培养条件进一步提高生产滴度。值得注意的是，在优化的培养条件下，在补料分批发酵中，最终的叶黄素菌株产生了 218.0 mg l ^-1的叶黄素，生产率为 5.01 mg l ^-1  h ^{-1 。}