A bacterial platform for fermentative production of plant alkaloids.
A bacterial platform for fermentative production of plant alkaloids.
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DOI：
10.1038/ncomms1327
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发表时间：
2011
影响因子：
16.6
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中科院分区：
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高等植物的次生代谢产物包括多种化学物质，如生物碱、异戊二烯类化合物和酚类化合物(苯丙类和类黄酮类)。虽然这些化合物在人类健康和营养方面有着广泛的应用，但目前它们主要是从植物中提取，由于这些代谢物大多在植物细胞中低水平积累，因此提取产率很低。合成生物学和代谢工程的最新进展使在微生物中定制生产植物次生代谢物成为可能，但这些方法通常需要添加昂贵的底物。在这里，我们开发了一个大肠杆菌发酵系统，它可以从简单的碳源产生植物生物碱，使用选定的酶来构建定制的生物合成途径。在该系统中，工程细胞在不添加底物的生长介质中培养产生植物苄基异喹啉生物碱(S)-网状生物碱(产量，46.0mgL −1培养基)。这里描述的发酵平台为低成本生产多种生物碱提供了机会。次生代谢物广泛用于人类健康和营养，但从植物中提取的产量往往很低。Nakagawa等人。对大肠杆菌的新陈代谢进行了改造，以开发一种利用简单碳源生产植物生物碱的发酵系统。
The secondary metabolites of higher plants include diverse chemicals, such as alkaloids, isoprenoids and phenolic compounds (phenylpropanoids and flavonoids). Although these compounds are widely used in human health and nutrition, at present they are mainly obtained by extraction from plants and extraction yields are low because most of these metabolites accumulate at low levels in plant cells. Recent advances in synthetic biology and metabolic engineering have enabled tailored production of plant secondary metabolites in microorganisms, but these methods often require the addition of expensive substrates. Here we develop an Escherichia coli fermentation system that yields plant alkaloids from simple carbon sources, using selected enzymes to construct a tailor-made biosynthetic pathway. In this system, engineered cells cultured in growth medium without additional substrates produce the plant benzylisoquinoline alkaloid, (S)-reticuline (yield, 46.0 mg l−1 culture medium). The fermentation platform described here offers opportunities for low-cost production of many diverse alkaloids. Secondary metabolites are widely used in human health and nutrition, but extraction yields from plants are often low. Nakagawa et al. have engineered the metabolism of Escherichia coli to develop a fermentation system that produces plant alkaloids from simple carbon sources.