Development of an artificial biosynthetic pathway for biosynthesis of (S)-reticuline based on HpaBC in engineered Escherichia coli,Biotechnology and Bioengineering

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Development of an artificial biosynthetic pathway for biosynthesis of (S)-reticuline based on HpaBC in engineered Escherichia coli
Biotechnology and Bioengineering ( IF 3.5 ) Pub Date : 2021-08-24 , DOI: 10.1002/bit.27924
Daoyi Guo ₁ , Sijia Kong ₁ , Yue Sun ₁ , Xun Li ₁ , Hong Pan ₁

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Benzylisoquinoline alkaloids (BIAs) are an important class of plant secondary metabolites with a variety of pharmacological activities. Although they are widely used, traditionally these compounds are extracted from natural sources because their structure is too complicated to achieve economically feasible chemical synthesis. Thus, microbial biosynthesis of BIAs is expected to reduce dependence on natural extracts. (S)-Reticuline is an important precursor for BIAs biosynthesis. Therefore, it is an attractive engineering target. In this study, we reported the development of a novel (S)-reticuline biosynthetic pathway based on 4-hydroxyphenylacetate 3-hydroxylase (HpaBC) in Escherichia coli. Then, we further improved the (S)-reticuline production to 307 ± 26.8 mg/L by increasing the availability of the precursor 3, 4-dihydroxyphenylacetaldehyde. The E. coli cell factory developed in this study can be used as a potential platform for further efficient biosynthesis of BIAs derivatives.

中文翻译：

基于HpaBC在工程大肠杆菌中生物合成(S)-网状菊碱的人工生物合成途径的开发

苄基异喹啉生物碱（BIAs）是一类重要的植物次生代谢产物，具有多种药理活性。尽管它们被广泛使用，但传统上这些化合物是从天然来源中提取的，因为它们的结构过于复杂，无法实现经济上可行的化学合成。因此，BIAs 的微生物生物合成有望减少对天然提取物的依赖。( S )-Reticuline 是 BIAs 生物合成的重要前体。因此，它是一个有吸引力的工程目标。在这项研究中，我们报道了在大肠杆菌中开发了一种基于 4-羟基苯乙酸 3-羟化酶 (HpaBC)的新型 ( S )-reticuline 生物合成途径。然后，我们进一步改进了（S)-reticuline 产量通过增加前体 3, 4-二羟基苯乙醛的可用性提高到 307 ± 26.8 mg/L。本研究中开发的大肠杆菌细胞工厂可作为进一步高效生物合成 BIAs 衍生物的潜在平台。

更新日期：2021-08-24

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