Biochemical Engineering Group, Plant Biochemistry Section, Department of Plant and Environmental Sciences, University of Copenhagen, Thorvaldsensvej 40, 1871, Frederiksberg C, Denmark.
Department of Bioengineering, McGill University, McConnell Engineering Building, 3480 University, Room 350, Montreal, QC, H3A 0E9, Canada.
Nat Commun. 2022 Sep 3;13(1):5188. doi: 10.1038/s41467-022-32921-w.
Humankind relies on specialized metabolites for medicines, flavors, fragrances, and numerous other valuable biomaterials. However, the chemical space occupied by specialized metabolites, and, thus, their application potential, is limited because their biosynthesis is based on only a handful of building blocks. Engineering organisms to synthesize alternative building blocks will bypass this limitation and enable the sustainable production of molecules with non-canonical chemical structures, expanding the possible applications. Herein, we focus on isoprenoids and combine synthetic biology with protein engineering to construct yeast cells that synthesize 10 non-canonical isoprenoid building blocks with 16 carbon atoms. We identify suitable terpene synthases to convert these building blocks into C scaffolds and a cytochrome P450 to decorate the terpene scaffolds and produce different oxygenated compounds. Thus, we reconstruct the modular structure of terpene biosynthesis on 16-carbon backbones, synthesizing 28 different non-canonical terpenes, some of which have interesting odorant properties.
人类依赖于特殊代谢物来生产药物、香料、香精以及许多其他有价值的生物材料。然而，由于特殊代谢物的生物合成仅基于少数几种构建块，因此它们所占据的化学空间及其应用潜力是有限的。通过工程化生物体来合成替代的构建块将绕过这一限制，实现具有非典型化学结构分子的可持续生产，从而扩展可能的应用。在这里，我们专注于异戊二烯，并将合成生物学与蛋白质工程相结合，构建能够合成 10 种具有 16 个碳原子的非典型异戊二烯构建块的酵母细胞。我们鉴定了合适的萜烯合酶，以将这些构建块转化为 C 支架，并使用细胞色素 P450 对萜烯支架进行修饰，从而产生不同的含氧化合物。因此，我们在 16 碳骨架上重建了萜烯生物合成的模块化结构，合成了 28 种不同的非典型萜烯，其中一些具有有趣的气味特性。
