Distributing a metabolic pathway among a microbial consortium enhances production of natural products.
Distributing a metabolic pathway among a microbial consortium enhances production of natural products.
复制标题
DOI：
10.1038/nbt.3095
复制
发表时间：
2015-04
影响因子：
46.9
通讯作者：
Stephanopoulos G
中科院分区：
文献类型：
--
作者：
Zhou K;Qiao K;Edgar S;Stephanopoulos G
代谢工程的微生物，如大肠杆菌和酿酒酵母生产高价值的天然代谢产物，往往是通过功能重建的长代谢途径。当通路的一部分需要特殊的环境或隔间来实现最佳功能时，就会出现问题。在这里，我们通过工程生物的共培养来解决这个问题，每个生物都包含最适合宿主的途径部分。在一个例子中，我们将乙酰化二醇紫杉醇前体的合成途径分为两个模块，在S. cerevisiae或E.大肠杆菌，这两种都不能自己产生紫杉醇前体。通过设计两种菌之间的互惠关系，在同一生物反应器中实现了稳定的共培养。使用大肠杆菌并通过酵母官能化。该合成聚生体产生33 mg/L含氧紫杉烷，包括单乙酰化双含氧紫杉烷。同样的方法也被用来生产丹参酮前体和功能化的倍半萜烯。
Metabolic engineering of microorganisms such as Escherichia coli and Saccharomyces cerevisiae to produce high-value natural metabolites is often done through functional reconstitution of long metabolic pathways. Problems arise when parts of pathways require specialized environments or compartments for optimal function. Here we solve this problem through co-culture of engineered organisms, each of which contains the part of the pathway that it is best suited to hosting. In one example, we divided the synthetic pathway for the acetylated diol paclitaxel precursor into two modules, expressed in either S. cerevisiae or E. coli, neither of which can produce the paclitaxel precursor on their own. Stable co-culture in the same bioreactor was achieved by designing a mutualistic relationship between the two species in which a metabolic intermediate produced by E. coli was used and functionalized by yeast. This synthetic consortium produced 33 mg/L oxygenated taxanes, including a monoacetylated dioxygenated taxane. The same method was also used to produce tanshinone precursors and functionalized sesquiterpenes.