Qiu Chenxi, Tao Huilin, Shen Yu, Qi Qingsheng, Hou Jin
State Key Laboratory of Microbial Technology, Shandong University, Binhai Road 72, Qingdao, Shandong 266237, P. R. China.
iScience. 2022 Dec 16;26(1):105817. doi: 10.1016/j.isci.2022.105817. eCollection 2023 Jan 20.
Acetyl-coenzyme A (Acetyl-CoA) and malonyl-coenzyme A (malonyl-CoA) are important precursors for producing various chemicals, and their availability affects the production of their downstream chemicals. Storage carbohydrates are considered important carbon and energy reservoirs. Herein, we find that regulating the storage carbohydrate synthesis improves metabolic fluxes toward malonyl-CoA. Interestingly, not only directly decreasing storage carbohydrate accumulation improved malonyl-CoA availability but also increasing the storage carbohydrate by overexpression enables an even higher production of acetyl-CoA- and malonyl-CoA-derived chemicals. We find that Ugp1p overexpression dynamically regulates the carbon flux to storage carbohydrate synthesis. In early exponential phases, Ugp1 overexpression causes more storage carbohydrate accumulation, while the carbon flux is then redirected toward acetyl-CoA and malonyl-CoA in later phases, thereby contributing to the synthesis of their derived products. Our study demonstrates the importance of storage carbohydrates rearrangement for the availability of acetyl-CoA and malonyl-CoA and therefore will facilitate the synthesis of their derived chemicals.
乙酰辅酶A（Acetyl-CoA）和丙二酰辅酶A（malonyl-CoA）是生产各种化学品的重要前体，它们的可利用性会影响其下游化学品的产量。储存碳水化合物被认为是重要的碳和能量储备。在此，我们发现调节储存碳水化合物的合成可改善朝向丙二酰辅酶A的代谢通量。有趣的是，不仅直接减少储存碳水化合物的积累可提高丙二酰辅酶A的可利用性，而且通过过表达增加储存碳水化合物也能使乙酰辅酶A和丙二酰辅酶A衍生化学品的产量更高。我们发现Ugp1p的过表达动态调节碳通量至储存碳水化合物的合成。在指数生长早期阶段，Ugp1的过表达导致更多储存碳水化合物的积累，而在后期阶段碳通量则重新导向乙酰辅酶A和丙二酰辅酶A，从而有助于它们衍生产品的合成。我们的研究证明了储存碳水化合物重排对于乙酰辅酶A和丙二酰辅酶A可利用性的重要性，因此将促进它们衍生化学品的合成。
