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在合成甲基营养型生物合成中辅助因子的挑战:生物工程和工业应用。

The cofactor challenge in synthetic methylotrophy: bioengineering and industrial applications.

机构信息

Charité - Universitätsmedizin Berlin, Department of Biochemistry, Charitéplatz 1, 10117 Berlin, Germany; Max Planck Institute of Molecular Plant Physiology, Am Mühlenberg 1, 14476 Potsdam, Germany; Max Planck Institute for Terrestrial Microbiology, Department of Biochemistry and Synthetic Metabolism, Karl-von-Frisch-Str. 10, 35043 Marburg, Germany.

Laboratory of Microbiology, Wageningen University, Stippeneng 4, 6708 WE Wageningen, The Netherlands.

出版信息

Curr Opin Biotechnol. 2023 Aug;82:102953. doi: 10.1016/j.copbio.2023.102953. Epub 2023 Jun 13.

DOI:10.1016/j.copbio.2023.102953
PMID:37320962
Abstract

Methanol is a promising feedstock for industrial bioproduction: it can be produced renewably and has high solubility and limited microbial toxicity. One of the key challenges for its bio-industrial application is the first enzymatic oxidation step to formaldehyde. This reaction is catalysed by methanol dehydrogenases (MDH) that can use NAD, O or pyrroloquinoline quinone (PQQ) as an electron acceptor. While NAD-dependent MDH are simple to express and have the highest energetic efficiency, they exhibit mediocre kinetics and poor thermodynamics at ambient temperatures. O-dependent methanol oxidases require high oxygen concentrations, do not conserve energy and thus produce excessive heat as well as toxic HO. PQQ-dependent MDH provide a good compromise between energy efficiency and good kinetics that support fast growth rates without any drawbacks for process engineering. Therefore, we argue that this enzyme class represents a promising solution for industry and outline engineering strategies for the implementation of these complex systems in heterologous hosts.

摘要

甲醇是一种很有前途的工业生物生产原料

它可以可再生,具有高溶解度和有限的微生物毒性。其生物工业应用的关键挑战之一是将甲醇转化为甲醛的第一步酶促氧化反应。该反应由甲醇脱氢酶(MDH)催化,其可以使用 NAD、O 或吡咯喹啉醌(PQQ)作为电子受体。虽然 NAD 依赖性 MDH 易于表达且具有最高的能量效率,但它们在环境温度下表现出中等的动力学和较差的热力学性质。O 依赖性甲醇氧化酶需要高氧浓度,不能节约能量,因此会产生过多的热量和有毒的 HO。PQQ 依赖性 MDH 在能量效率和良好动力学之间提供了良好的折衷,支持快速生长速率,而不会对工艺工程造成任何缺点。因此,我们认为该酶类代表了工业的一种很有前途的解决方案,并概述了在异源宿主中实施这些复杂系统的工程策略。

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