An automated Design-Build-Test-Learn pipeline for enhanced microbial production of fine chemicals.
An automated Design-Build-Test-Learn pipeline for enhanced microbial production of fine chemicals.
复制标题
DOI：
10.1038/s42003-018-0076-9
复制
发表时间：
2018
影响因子：
5.9
通讯作者：
Scrutton NS
中科院分区：
文献类型：
--
作者：
Carbonell P;Jervis AJ;Robinson CJ;Yan C;Dunstan M;Swainston N;Vinaixa M;Hollywood KA;Currin A;Rattray NJW;Taylor S;Spiess R;Sung R;Williams AR;Fellows D;Stanford NJ;Mulherin P;Le Feuvre R;Barran P;Goodacre R;Turner NJ;Goble C;Chen GG;Kell DB;Micklefield J;Breitling R;Takano E;Faulon JL;Scrutton NS
精细化学品的微生物生产提供了一种有前途的生物可持续制造解决方案，导致了越来越多的天然产品和高价值化学品的成功生产。但是，工业一级的发展由于需要大量的资源投资而受到阻碍。在这里，我们提出了一个集成的设计-构建-测试-学习（DBTL）管道，用于发现和优化生物合成途径，该管道被设计为化合物不可知论和自动化。我们最初应用该管道在大肠杆菌中生产黄酮类化合物(2S)-匹诺匹林，以证明每个阶段快速迭代的DBTL循环自动化。在这种情况下，应用两个DBTL循环成功地建立了生产途径，提高了500倍，竞争滴度高达88 mg L−1。该管道在优化生物碱途径中的进一步应用表明，它如何促进微生物菌株的快速优化，以生产任何感兴趣的化合物。Pablo Carbonell等人提出了一种自动化管道，用于发现和优化微生物生产精细化学品的生物合成途径。他们将他们的管道应用于大肠杆菌中类黄酮(2S)-匹诺曹蛋白的生产，并显示该途径改善了500倍。
The microbial production of fine chemicals provides a promising biosustainable manufacturing solution that has led to the successful production of a growing catalog of natural products and high-value chemicals. However, development at industrial levels has been hindered by the large resource investments required. Here we present an integrated Design–Build-Test–Learn (DBTL) pipeline for the discovery and optimization of biosynthetic pathways, which is designed to be compound agnostic and automated throughout. We initially applied the pipeline for the production of the flavonoid (2S)-pinocembrin in Escherichia coli, to demonstrate rapid iterative DBTL cycling with automation at every stage. In this case, application of two DBTL cycles successfully established a production pathway improved by 500-fold, with competitive titers up to 88 mg L−1. The further application of the pipeline to optimize an alkaloids pathway demonstrates how it could facilitate the rapid optimization of microbial strains for production of any chemical compound of interest. Pablo Carbonell et al. present an automated pipeline for the discovery and optimization of biosynthetic pathways for microbial production of fine chemicals. They apply their pipeline to the production of the flavonoid (2S)-pinocembrin in Escherichia coli and show improvement of the pathway by 500-fold.
登录
查看更多内容
影响因子：
11.9
作者：
Carbonell P;Currin A;Jervis AJ;Rattray NJ;Swainston N;Yan C;Takano E;Breitling R
通讯作者：
Breitling R
影响因子：
3.7
作者：
Engler, Carola;Kandzia, Romy;Marillonnet, Sylvestre
通讯作者：
Marillonnet, Sylvestre
DOI：
10.1007/978-1-4939-6343-0_8
发表时间：
2017-01-01
期刊：
SYNTHETIC DNA: METHODS AND PROTOCOLS
影响因子：
--
作者：
Chandran, Sunil
通讯作者：
Chandran, Sunil
影响因子：
4.7
作者：
de Kok, Stefan;Stanton, Leslie H.;Chandran, Sunil S.
通讯作者：
Chandran, Sunil S.
影响因子：
5.8
作者：
Carbonell, Pablo;Wong, Jerry;Faulon, Jean-Loup
通讯作者：
Faulon, Jean-Loup