聚酮
对接(动物)
酶
虾青素
装配线
合成生物学
代谢工程
大肠杆菌
生物化学
生物
化学
计算生物学
生物合成
基因
医学
机械工程
护理部
工程类
类胡萝卜素
作者
Xiaopeng Sun,Yujie Yuan,Qitong Chen,Shiqi Nie,Jianhua Guo,Zutian Ou,Min Huang,Zixin Deng,Tiangang Liu,Tian Ma
标识
DOI:10.1038/s41467-022-33272-2
摘要
Abstract Engineered metabolic pathways in microbial cell factories often have no natural organization and have challenging flux imbalances, leading to low biocatalytic efficiency. Modular polyketide synthases (PKSs) are multienzyme complexes that synthesize polyketide products via an assembly line thiotemplate mechanism. Here, we develop a strategy named mimic PKS enzyme assembly line (mPKSeal) that assembles key cascade enzymes to enhance biocatalytic efficiency and increase target production by recruiting cascade enzymes tagged with docking domains from type I cis -AT PKS. We apply this strategy to the astaxanthin biosynthetic pathway in engineered Escherichia coli for multienzyme assembly to increase astaxanthin production by 2.4-fold. The docking pairs, from the same PKSs or those from different cis -AT PKSs evidently belonging to distinct classes, are effective enzyme assembly tools for increasing astaxanthin production. This study addresses the challenge of cascade catalytic efficiency and highlights the potential for engineering enzyme assembly.
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