Institute for Quantitative Biology, Biochemistry and Biotechnology, School of Biological Sciences, University of Edinburgh, King's Buildings, Alexander Crum Brown Road, Edinburgh, EH9 3FF, UK.
School of Chemistry, University of Edinburgh, Joseph Black Building, David Brewster Road, King's Buildings, Edinburgh, EH9 3FJ, UK.
Angew Chem Int Ed Engl. 2019 Sep 2;58(36):12409-12414. doi: 10.1002/anie.201903973. Epub 2019 Aug 7.
Microorganisms can be programmed to perform chemical synthesis via metabolic engineering. However, despite an increasing interest in the use of de novo metabolic pathways and designer whole-cells for small molecule synthesis, the inherent synthetic capabilities of native microorganisms remain underexplored. Herein, we report the use of unmodified E. coli BL21(DE3) cells for the reduction of keto-acrylic compounds and apply this whole-cell biotransformation to the synthesis of aminolevulinic acid from a lignin-derived feedstock. The reduction reaction is rapid, chemo-, and enantioselective, occurs under mild conditions (37 °C, aqueous media), and requires no toxic transition metals or external reductants. This study demonstrates the remarkable promiscuity of central metabolism in bacterial cells and how these processes can be leveraged for synthetic chemistry without the need for genetic manipulation.
微生物可以通过代谢工程来进行化学合成。然而，尽管人们越来越感兴趣地利用从头设计的代谢途径和工程化的全细胞来进行小分子的合成，但天然微生物的固有合成能力仍未得到充分探索。在此，我们报告了使用未经修饰的大肠杆菌 BL21(DE3)细胞来还原酮-丙烯酸化合物，并将这种全细胞生物转化应用于从木质素衍生的原料中合成氨基酮戊酸。该还原反应快速、化学选择性和对映选择性强，在温和的条件下（37°C，水相介质）进行，且不需要有毒的过渡金属或外部还原剂。本研究展示了细菌细胞中中心代谢的惊人的混杂性，以及如何在无需遗传操作的情况下利用这些过程进行合成化学。
