合成生物学
代谢工程
生产(经济)
化学
代谢途径
粘酸
漏斗
生化工程
生物化学
计算生物学
生物技术
生物
新陈代谢
有机化学
酶
工程类
尿
宏观经济学
经济
作者
Brian Thompson,Shawn Pugh,Michael Machas,David R. Nielsen
标识
DOI:10.1021/acssynbio.7b00331
摘要
Muconic acid is a promising platform biochemical and precursor to adipic acid, which can be used to synthesize various plastics and polymers. In this study, the systematic construction and comparative evaluation of a modular network of non-natural pathways for muconic acid biosynthesis was investigated in Escherichia coli, including via three distinct and novel pathways proceeding via phenol as a common intermediate. However, poor recombinant activity and high promiscuity of phenol hydroxylase ultimately limited "phenol-dependent" muconic acid production. A fourth pathway proceeding via p-hydroxybenzoate, protocatechuate, and catechol was accordingly developed, though with muconic acid titers by this route reaching just 819 mg/L, its performance lagged behind that of the established, "3-dehydroshikimiate-derived" route. Finally, these two most promising pathways were coexpressed in parallel to create a synthetic "metabolic funnel" that, by enabling maximal net precursor assimilation and flux while preserving native chorismate biosynthesis, nearly doubled muconic acid production to up to >3.1 g/L at a glucose yield of 158 mg/g while introducing only a single auxotrophy. This generalizable, "funneling" strategy is expected to have broad applications in metabolic engineering for further enhancing production of muconic acid, as well as other important bioproducts of interest.
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