Alternative metabolic pathways and strategies to high-titre terpenoid production in Escherichia coli.
Alternative metabolic pathways and strategies to high-titre terpenoid production in Escherichia coli.
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DOI：
10.1039/d1np00025j
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发表时间：
2022-01-26
影响因子：
11.9
通讯作者：
Scrutton NS
中科院分区：
文献类型：
--
作者：
Rinaldi MA;Ferraz CA;Scrutton NS
涵盖：到2021年萜类化合物是广泛应用于各种行业的一组不同的化学品。微生物萜类化合物生产有可能用可再生工艺取代这些化合物的传统制造，但需要进一步改进滴度以达到成本竞争力。这篇综述讨论了增加大肠杆菌中萜类化合物滴度的策略，重点是替代代谢途径。替代途径可通过以下途径提高滴度：为重定向碳通量的天然代谢提供更高的正交性；避免有毒中间体；绕过高度管制或瓶颈步骤；或更短因而更有效和更容易操作。典型的2- c -甲基-d-赤藓糖醇4-磷酸（MEP）和甲羟戊酸（MVA）途径被设计为增加滴度，有时使用来自不同物种的同源物来解决瓶颈。此外，替代萜类化合物途径，包括MEP和MVA途径的额外入口点，古菌MVA途径和新的人工途径，为提高滴度提供了新的工具。戊烯基二磷酸合成酶延长萜类链，替代同源物创造正交途径，增加产品多样性。萜类合成酶和修饰酶的替代来源也可以更适合大肠杆菌的表达。挖掘越来越多的细菌基因组，寻找新的细菌萜类合成酶和修饰酶，识别出优于真核生物合成酶的酶，并扩大微生物萜类生产的多样性。从细胞中去除萜类化合物在生产中也至关重要，因此萜类化合物的回收和处理最终产物毒性的方法增加了滴度。综合起来，这些策略有助于目前努力增加微生物萜类化合物的生产，使其具有商业可行性。萜类化合物是一种广泛应用于工业领域的化学物质。它们可以通过替代的代谢途径来达到生物制造的更高要求。
Covering: up to 2021 Terpenoids are a diverse group of chemicals used in a wide range of industries. Microbial terpenoid production has the potential to displace traditional manufacturing of these compounds with renewable processes, but further titre improvements are needed to reach cost competitiveness. This review discusses strategies to increase terpenoid titres in Escherichia coli with a focus on alternative metabolic pathways. Alternative pathways can lead to improved titres by providing higher orthogonality to native metabolism that redirects carbon flux, by avoiding toxic intermediates, by bypassing highly-regulated or bottleneck steps, or by being shorter and thus more efficient and easier to manipulate. The canonical 2-C-methyl-d-erythritol 4-phosphate (MEP) and mevalonate (MVA) pathways are engineered to increase titres, sometimes using homologs from different species to address bottlenecks. Further, alternative terpenoid pathways, including additional entry points into the MEP and MVA pathways, archaeal MVA pathways, and new artificial pathways provide new tools to increase titres. Prenyl diphosphate synthases elongate terpenoid chains, and alternative homologs create orthogonal pathways and increase product diversity. Alternative sources of terpenoid synthases and modifying enzymes can also be better suited for E. coli expression. Mining the growing number of bacterial genomes for new bacterial terpenoid synthases and modifying enzymes identifies enzymes that outperform eukaryotic ones and expand microbial terpenoid production diversity. Terpenoid removal from cells is also crucial in production, and so terpenoid recovery and approaches to handle end-product toxicity increase titres. Combined, these strategies are contributing to current efforts to increase microbial terpenoid production towards commercial feasibility. Terpenoids are a diverse group of chemicals used in a wide range of industries. They can be made through alternative metabolic pathways to reach the higher needed for biomanufacturing.
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影响因子：
4.1
作者：
Aguilar F;Ekramzadeh K;Scheper T;Beutel S
通讯作者：
Beutel S
DOI：
10.1126/science.1191652
发表时间：
2010-10-01
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Ajikumar PK;Xiao WH;Tyo KE;Wang Y;Simeon F;Leonard E;Mucha O;Phon TH;Pfeifer B;Stephanopoulos G
通讯作者：
Stephanopoulos G
影响因子：
2.9
作者：
Andreassi, JL;Dabovic, K;Leyh, TS
通讯作者：
Leyh, TS
影响因子：
5.8
作者：
Carbonell, Pablo;Wong, Jerry;Faulon, Jean-Loup
通讯作者：
Faulon, Jean-Loup
DOI：
10.1039/p19820000949
发表时间：
1982-01-01
期刊：
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1
影响因子：
--
作者：
ATTYGALLE, AB;MORGAN, ED
通讯作者：
MORGAN, ED