Institute of Bioprocess and Biosystems Engineering, Hamburg University of Technology, Denickestr. 15, 21071, Hamburg, Germany,
Adv Biochem Eng Biotechnol. 2013;137:41-65. doi: 10.1007/10_2013_221.
: The construction of efficient enzyme complexes for multienzymatic biosynthesis is of increasing interest in order to achieve maximum yield and to minimize the interference due to shortcomings that are typical for straightforward one-pot multienzyme catalysis. These include product or intermediate feedback inhibition, degeneration, and diffusive losses of reaction intermediates, consumption of co-factors, and others. The main mechanisms in nature to tackle these effects in transient or stable protein associations are the formation of metabolic channeling and microcompartments, processes that are desirable also for multienzymatic biosynthesis in vitro. This chapter provides an overview over two main aspects. First, numerous recent strategies for establishing compartmentalized multienzyme associations and constructed synthetic enzyme complexes are reviewed. Second, the computational methods at hand to investigate and optimize such associations systematically, especially with focus on large multienzyme complexes and metabolic channeling, are discussed. Perspectives on future studies of multienzymatic biosynthesis concerning compartmentalization and metabolic channeling are presented.
高效酶复合物在多酶生物合成中的构建越来越受到关注，目的是实现最大产量，并将由于直接一锅多酶催化的典型缺点造成的干扰最小化。这些缺点包括产物或中间产物的反馈抑制、退化和反应中间产物的扩散损失、辅助因子的消耗等。在瞬时或稳定的蛋白质复合物中，自然界中解决这些问题的主要机制是形成代谢沟道和微区隔，这些过程也是体外多酶生物合成所需要的。本章概述了两个主要方面。首先，综述了最近建立分隔多酶关联和构建合成酶复合物的许多策略。其次，讨论了目前用于系统地研究和优化这种关联的计算方法，特别是重点关注大型多酶复合物和代谢沟道。提出了关于多酶生物合成中分隔和代谢沟道的未来研究展望。
