Engineering the unicellular alga Phaeodactylum tricornutum for high-value plant triterpenoid production.
Engineering the unicellular alga Phaeodactylum tricornutum for high-value plant triterpenoid production.
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DOI：
10.1111/pbi.12948
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发表时间：
2019-01
影响因子：
13.8
通讯作者：
Matthijs M
中科院分区：
文献类型：
--
作者：
D'Adamo S;Schiano di Visconte G;Lowe G;Szaub-Newton J;Beacham T;Landels A;Allen MJ;Spicer A;Matthijs M
植物三萜类化合物构成了多种有机化合物，在发育、植物防御和环境相互作用中发挥着重要作用。几种三萜已显示出作为药物的潜力。一个例子是桦木醇，它已显示出作为治疗某些癌症和艾滋病毒的药物前体的前景。三萜类化合物商业化的主要挑战包括其生产水平低以及从天然宿主中存在的复杂混合物中进行经济有效的纯化。因此，在工业相关微生物系统（例如细菌和酵母）中生产这些化合物的尝试引起了人们的极大兴趣。在这里，我们报道了光合硅藻三角褐指藻（一种单细胞真核藻类）中三萜桦木醇及其前体羽扇豆醇的生产。这是通过在微藻中引入三种植物酶来实现的：莲花氧化角鲨烯环化酶和蒺藜苜蓿细胞色素 P450 及其天然还原酶。 L. japonicus 氧化角鲨烯环化酶的引入扰乱了天然甲羟戊酸和甾醇生物合成途径的 mRNA 表达水平。选择表现最好的菌株并在 550 L 中试规模光生物反应器设施中生长。据我们所知，这是在硅藻中进行的最广泛的途径工程，也是首次在微藻中人工生产皂苷元，证明了在微藻中光生物生产更复杂的高价值代谢物的可行性。
Plant triterpenoids constitute a diverse class of organic compounds that play a major role in development, plant defence and environmental interaction. Several triterpenes have demonstrated potential as pharmaceuticals. One example is betulin, which has shown promise as a pharmaceutical precursor for the treatment of certain cancers and HIV. Major challenges for triterpenoid commercialization include their low production levels and their cost‐effective purification from the complex mixtures present in their natural hosts. Therefore, attempts to produce these compounds in industrially relevant microbial systems such as bacteria and yeasts have attracted great interest. Here, we report the production of the triterpenes betulin and its precursor lupeol in the photosynthetic diatom Phaeodactylum tricornutum, a unicellular eukaryotic alga. This was achieved by introducing three plant enzymes in the microalga: a Lotus japonicus oxidosqualene cyclase and a Medicago truncatula cytochrome P450 along with its native reductase. The introduction of the L. japonicus oxidosqualene cyclase perturbed the mRNA expression levels of the native mevalonate and sterol biosynthesis pathway. The best performing strains were selected and grown in a 550‐L pilot‐scale photobioreactor facility. To our knowledge, this is the most extensive pathway engineering undertaken in a diatom and the first time that a sapogenin has been artificially produced in a microalga, demonstrating the feasibility of the photo‐bio‐production of more complex high‐value, metabolites in microalgae.
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DOI：
10.1111/nph.13996
发表时间：
2016-09
期刊：
The New phytologist
影响因子：
--
作者：
Andre CM;Legay S;Deleruelle A;Nieuwenhuizen N;Punter M;Brendolise C;Cooney JM;Lateur M;Hausman JF;Larondelle Y;Laing WA
通讯作者：
Laing WA
影响因子：
11.6
作者：
Cerutti, H;Johnson, AM;Boynton, JE
通讯作者：
Boynton, JE
影响因子：
5.2
作者：
Gimpel JA;Henríquez V;Mayfield SP
通讯作者：
Mayfield SP
影响因子：
6.4
作者：
Hempel F;Bozarth AS;Lindenkamp N;Klingl A;Zauner S;Linne U;Steinbüchel A;Maier UG
通讯作者：
Maier UG
影响因子：
46.9
作者：
Dueber, John E.;Wu, Gabriel C.;Keasling, Jay D.
通讯作者：
Keasling, Jay D.