Metabolic engineering of tomato fruit enriched in L-DOPA.
Metabolic engineering of tomato fruit enriched in L-DOPA.
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DOI：
10.1016/j.ymben.2020.11.011
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发表时间：
2021-05
影响因子：
8.4
通讯作者：
Martin C
中科院分区：
文献类型：
--
作者：
Breitel D;Brett P;Alseekh S;Fernie AR;Butelli E;Martin C
左旋多巴，也称为左旋多巴或L-3，4-二羟基苯丙氨酸，是一种非标准氨基酸，是治疗帕金森病（PD）的金标准药物。最近，在甜菜根BvCYP 76 AD 6中鉴定了编码负责其合成的酶的基因，该酶是有色色素组甜菜色素的前体。我们已经通过以水果特异性方式过表达BvCYP 76 AD 6来工程化富含L-DOPA的番茄果实。对转基因果实的分析揭示了在非天然产生甜菜色素的植物中积累L-DOPA的可行性。果实积累L-DOPA也表现出对果实代谢组的主要影响。其中一些变化包括氨基酸水平升高、TCA和糖酵解途径中间体水平变化以及酚类化合物和含氮专门代谢物水平降低。此外，我们能够通过提高代谢主调节剂MYB 12的表达，特别是在番茄果实中，与BvCYP 76 AD 6一起，进一步增加L-DOPA水平。我们的研究阐明了L-DOPA在植物中的新作用，因为它影响水果质量参数，包括抗氧化能力和硬度。在番茄果实中达到的L-DOPA水平与L-DOPA积累植物的其他非种子器官中的水平相当，这提供了通过扩大L-DOPA积累植物的库来开发L-DOPA的新生物来源的机会。这些番茄果实可以作为这种重要药物的替代来源。番茄果实被工程化以合成和积累L-DOPA。转录因子MYB 12的共表达使番茄果实中的左旋多巴水平加倍。左旋多巴的积累导致番茄中初级和次级代谢产物谱的额外变化。左旋多巴番茄果实表现出改善的货架期和降低的灰葡萄孢的易感性。
L-DOPA, also known as Levodopa or L-3,4-dihydroxyphenylalanine, is a non-standard amino acid, and the gold standard drug for the treatment for Parkinson's Disease (PD). Recently, a gene encoding the enzyme that is responsible for its synthesis, as a precursor of the coloured pigment group betalains, was identified in beetroot, BvCYP76AD6. We have engineered tomato fruit enriched in L-DOPA through overexpression of BvCYP76AD6 in a fruit specific manner. Analysis of the transgenic fruit revealed the feasibility of accumulating L-DOPA in a non-naturally betalain-producing plant. Fruit accumulating L-DOPA also showed major effects on the fruit metabolome. Some of these changes included elevation of amino acids levels, changes in the levels of intermediates of the TCA and glycolysis pathways and reductions in the levels of phenolic compounds and nitrogen-containing specialised metabolites. Furthermore, we were able to increase the L-DOPA levels further by elevating the expression of the metabolic master regulator, MYB12, specifically in tomato fruit, together with BvCYP76AD6. Our study elucidated new roles for L-DOPA in plants, because it impacted fruit quality parameters including antioxidant capacity and firmness. The L-DOPA levels achieved in tomato fruit were comparable to the levels in other non-seed organs of L-DOPA - accumulating plants, offering an opportunity to develop new biological sources of L-DOPA by widening the repertoire of L-DOPA-accumulating plants. These tomato fruit could be used as an alternative source of this important pharmaceutical. Tomato fruit were engineered to synthesise and accumulate L-DOPA. Co-expression of the transcription factor, MYB12, doubled the levels of L-DOPA in tomato fruit. The accumulation of L-DOPA resulted in additional changes in the profile of primary and secondary metabolites in tomatoes. The L-DOPA tomato fruit exhibited improved shelf life and reduced susceptibility to Botrytis cinerea.
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影响因子：
2.3
作者：
Hachinohe, M;Matsumoto, H
通讯作者：
Matsumoto, H
影响因子：
9.4
作者：
Bassolino, Laura;Zhang, Yang;Martin, Cathie
通讯作者：
Martin, Cathie
影响因子：
7.2
作者：
Itkin, Maxim;Seybold, Heike;Aharoni, Asaph
通讯作者：
Aharoni, Asaph
影响因子：
5.3
作者：
Exposito-Rodriguez, Marino;Borges, Andres A.;Borges-Perez, Andres;Perez, Jose A.
通讯作者：
Perez, Jose A.
番茄功能基因组学数据库：番茄功能基因组学的综合资源和分析软件包。
影响因子：
14.9
作者：
Fei Z;Joung JG;Tang X;Zheng Y;Huang M;Lee JM;McQuinn R;Tieman DM;Alba R;Klee HJ;Giovannoni JJ
通讯作者：
Giovannoni JJ