作为下一代代谢工程工具的细菌微隔室:利用大自然的解决方案限制具有挑战性的分解途径。

IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Lior Doron, Cheryl A Kerfeld
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引用次数: 0

摘要

合成生物学的进步促进了将异源代谢途径纳入各种细菌底盘,从而合成目标生物产品。然而,异源生产途径的总产出可能会受到低通量、酶杂乱性、有毒中间体的形成或竞争反应中间体损失等问题的影响,最终阻碍其潜力的充分发挥。以蛋白质为基础的自组装、易修饰细菌微区(BMCs)提供了一种克服这些障碍的复杂方法,它作为一个自主催化模块,与细胞的调控和代谢网络脱钩。十多年来,对各种类型 BMC 的基础研究,特别是对 BMC 外壳及其自组装的结构研究、BMC 外壳支架上酶的招募以及辅助蛋白(如转运体、调节器和激活酶)参与 BMC 与细胞代谢整合的研究,极大地推动了该领域的发展。这些进展使生物工程人员能够设计出合成的多酶 BMC,以促进乙醇或氢的产生,提高细胞的多磷酸盐水平,并将甘油转化为丙二醇或将甲酸转化为丙酮酸。这些开创性的工作证明了合成 BMC 在封装非本地多酶生化途径以合成高价值产品方面的巨大潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Bacterial microcompartments as a next-generation metabolic engineering tool: utilizing nature's solution for confining challenging catabolic pathways.

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.

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来源期刊
Biochemical Society transactions
Biochemical Society transactions 生物-生化与分子生物学
CiteScore
7.80
自引率
0.00%
发文量
351
审稿时长
3-6 weeks
期刊介绍: Biochemical Society Transactions is the reviews journal of the Biochemical Society. Publishing concise reviews written by experts in the field, providing a timely snapshot of the latest developments across all areas of the molecular and cellular biosciences. Elevating our authors’ ideas and expertise, each review includes a perspectives section where authors offer comment on the latest advances, a glimpse of future challenges and highlighting the importance of associated research areas in far broader contexts.
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