The design of novel metabolic pathways for efficient biosynthesis of natural products has received much interest, but often lacks systematic approach and chemistry-based guideline. Here we propose carbon skeleton reconstruction based on retrobiosynthetic design as a new approach and chemistry-guideline to solve the problem of properly matching precursors, one of the key issues for efficient biosynthesis. It is demonstrated for the development of an unnatural pathway for efficient biosynthesis of 5-aminolevulinic acid. The new pathway has several advantages compared to the existing natural ones such as high carbon utilization efficiency and orthogonality. It is particularly useful for overcoming the problem of glycine supply. The unnatural pathway is verified in vitro in an enzymatic cascade and in vivo in recombinant E. coli with an exogenous glyoxylate transaminase as a key enzyme.

中文翻译：

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基于逆向生物合成设计从乙醛酸酯高效合成5-氨基乙酰丙酸的非自然途径

用于有效合成天然产物的新型代谢途径的设计引起了人们的极大兴趣，但通常缺乏系统的方法和基于化学的指导。在这里，我们提出基于逆向生物合成设计的碳骨架重建作为一种新方法和化学指南，以解决前驱物正确匹配的问题，前驱物是有效生物合成的关键问题之一。它被证明可以有效地合成5-氨基乙酰丙酸的非天然途径。与现有的自然途径相比，新途径具有许多优势，例如高碳利用效率和正交性。对于克服甘氨酸供应问题特别有用。在体外以酶促级联反应验证了非天然途径，并且重组大肠杆菌的体内，以外源乙醛酸转氨酶为关键酶。