Abstract:
Advancements in synthetic biology have facilitated the incorporation of heterologous metabolic pathways into various bacterial chassis, leading to the synthesis of targeted bioproducts. However, total output from heterologous production pathways can suffer from low flux, enzyme promiscuity, formation of toxic intermediates, or intermediate loss to competing reactions, which ultimately hinder their full potential. The self-assembling, easy-to-modify, protein-based bacterial microcompartments (BMCs) offer a sophisticated way to overcome these obstacles by acting as an autonomous catalytic module decoupled from the cell\'s regulatory and metabolic networks. More than a decade of fundamental research on various types of BMCs, particularly structural studies of shells and their self-assembly, the recruitment of enzymes to BMC shell scaffolds, and the involvement of ancillary proteins such as transporters, regulators, and activating enzymes in the integration of BMCs into the cell\'s metabolism, has significantly moved the field forward. These advances have enabled bioengineers to design synthetic multi-enzyme BMCs to promote ethanol or hydrogen production, increase cellular polyphosphate levels, and convert glycerol to propanediol or formate to pyruvate. These pioneering efforts demonstrate the enormous potential of synthetic BMCs to encapsulate non-native multi-enzyme biochemical pathways for the synthesis of high-value products.
摘要:
合成生物学的进步促进了将异源代谢途径整合到各种细菌底盘中,导致目标生物产品的合成。然而,异源生产途径的总产出可能会受到低通量的影响,酶滥交,形成有毒中间体,或者竞争反应的中间损失,这最终阻碍了他们的全部潜力。自组装,易于修改,蛋白质为基础的细菌微室(BMC)提供了一种复杂的方法来克服这些障碍,作为一个自主的催化模块与细胞的调节和代谢网络分离。对各种类型的BMC进行了十多年的基础研究,特别是壳及其自组装的结构研究,酶对BMC外壳支架的募集,以及辅助蛋白如转运蛋白的参与,监管者,和激活酶的BMCs整合到细胞的代谢,大大推动了该领域的发展。这些进步使生物工程师能够设计合成的多酶BMC,以促进乙醇或氢气的生产,增加细胞多磷酸盐水平,并将甘油转化为丙二醇或将甲酸盐转化为丙酮酸盐。这些开创性的努力证明了合成BMC包封非天然多酶生化途径以合成高价值产品的巨大潜力。