Exploiting the Feedstock Flexibility of the Emergent Synthetic Biology Chassis Vibrio natriegens for Engineered Natural Product Production
Exploiting the Feedstock Flexibility of the Emergent Synthetic Biology Chassis Vibrio natriegens for Engineered Natural Product Production
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DOI：
10.3390/md17120679
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发表时间：
2019-12-01
期刊：
影响因子：
5.4
通讯作者：
Vora, Gary J.
中科院分区：
文献类型：
--
作者：
Ellis, Gregory A.;Tschirhart, Tanya;Vora, Gary J.
合成生物学最近的一个目标是确定新的底盘，提供模式生物缺乏的好处。产钠弧菌是一种海洋革兰氏阴性细菌，它是一种新兴的合成生物学底盘，具有固有的优点：极快的生长速度，遗传易处理性和在各种碳源上生长的能力（“原料灵活性”）。考虑到这些固有的好处，我们试图确定其异源生产天然产品的潜力，并选择β-胡萝卜素和紫罗兰素作为测试案例。对于β-胡萝卜素的生产，我们表达了来自姐妹海洋细菌Vibrio campbellii的β-胡萝卜素生物合成途径，以及来自革兰氏阳性细菌嗜酸乳杆菌的甲羟戊酸生物合成途径，以提高前体丰度。通过表达来源于紫色色杆菌的生物合成基因簇来产生紫色菌素。产钠弧菌不仅能够在丰富的培养基中异源地产生这些化合物，说明其作为小分子药物生产的新底盘的前景，而且它也在使用各种原料的基本培养基中这样做。产钠弧菌用多种工业相关原料生产天然产物的能力证明了继续研究在这种底盘中生产更复杂的天然产物。
A recent goal of synthetic biology has been to identify new chassis that provide benefits lacking in model organisms. Vibrio natriegens is a marine Gram-negative bacterium which is an emergent synthetic biology chassis with inherent benefits: An extremely fast growth rate, genetic tractability, and the ability to grow on a variety of carbon sources ("feedstock flexibility"). Given these inherent benefits, we sought to determine its potential to heterologously produce natural products, and chose beta-carotene and violacein as test cases. For beta-carotene production, we expressed the beta-carotene biosynthetic pathway from the sister marine bacterium Vibrio campbellii, as well as the mevalonate biosynthetic pathway from the Gram-positive bacterium Lactobacillus acidophilus to improve precursor abundance. Violacein was produced by expressing a biosynthetic gene cluster derived from Chromobacterium violaceum. Not only was V. natriegens able to heterologously produce these compounds in rich media, illustrating its promise as a new chassis for small molecule drug production, but it also did so in minimal media using a variety of feedstocks. The ability for V. natriegens to produce natural products with multiple industrially-relevant feedstocks argues for continued investigations into the production of more complex natural products in this chassis.