ATP drives direct photosynthetic production of 1-butanol in cyanobacteria
ATP drives direct photosynthetic production of 1-butanol in cyanobacteria
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DOI：
10.1073/pnas.1200074109
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发表时间：
2012-04-17
影响因子：
11.1
通讯作者：
Liao, James C.
中科院分区：
文献类型：
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作者：
Lan, Ethan I.;Liao, James C.
虽然ATP的保护通常是微生物生产化学品的理想特性，但我们证明了ATP的额外消耗可能有利于驱动非天然途径中的产品形成。虽然通过发酵辅酶A（CoA）依赖性途径使用β-氧化的逆转来生产1-丁醇存在于自然界中并且已经在各种生物体中得到证实，但是该途径的第一步，即两个乙酰辅酶A分子缩合为乙酰乙酰辅酶A，在药理学上是不利的。在这里，我们表明，人工设计的ATP消耗通过一个途径的修改可以推动这一反应向前，并使第一次直接光合生产的1-丁醇从蓝藻细长聚球藻PCC 7942。我们进一步证明，用单独的丁醛脱氢酶（Bldh）和NADPH依赖性醇脱氢酶（YqhD）取代双功能醛/醇脱氢酶（AdhE 2）使1-丁醇产量增加了4倍。这些结果证明了ATP和辅因子驱动力作为改变代谢通量的设计原则的重要性。
While conservation of ATP is often a desirable trait for microbial production of chemicals, we demonstrate that additional consumption of ATP may be beneficial to drive product formation in a nonnatural pathway. Although production of 1-butanol by the fermentative coenzyme A (CoA)-dependent pathway using the reversal of beta-oxidation exists in nature and has been demonstrated in various organisms, the first step of the pathway, condensation of two molecules of acetyl-CoA to acetoacetyl-CoA, is thermodynamically unfavorable. Here, we show that artificially engineered ATP consumption through a pathway modification can drive this reaction forward and enables for the first time the direct photosynthetic production of 1-butanol from cyanobacteria Synechococcus elongatus PCC 7942. We further demonstrated that substitution of bifunctional aldehyde/alcohol dehydrogenase (AdhE2) with separate butyraldehyde dehydrogenase (Bldh) and NADPH-dependent alcohol dehydrogenase (YqhD) increased 1-butanol production by 4-fold. These results demonstrated the importance of ATP and cofactor driving forces as a design principle to alter metabolic flux.