Discovery and Analysis of Novel Metabolic Pathways for the Biosynthesis of Industrial Chemicals: 3-Hydroxypropanoate
Discovery and Analysis of Novel Metabolic Pathways for the Biosynthesis of Industrial Chemicals: 3-Hydroxypropanoate
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DOI：
10.1002/bit.22673
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发表时间：
2010-06-15
影响因子：
3.8
通讯作者：
Hatzimanikatis, Vassily
中科院分区：
文献类型：
--
作者：
Henry, Christopher S.;Broadbelt, Linda J.;Hatzimanikatis, Vassily
可持续微生物生产高价值有机化合物，如3-羟基丙酸酯(3HP)，正成为替代利用石化原料的有机合成的一种越来越有吸引力的选择。我们应用生化网络集成计算探索者(BNICE)框架来自动化设计和评估丙酮酸生产3HP的新的生物合成路线。在BNICE框架产生的途径中，有所有生产3HP的已知途径以及许多新途径。根据四个标准对BNICE产生的途径进行了排序：途径长度、热力学可行性、从葡萄糖到3HP的最大可实现产率以及可产生3HP的最大可实现活性。从这一排名中，有四条途径被认为是最有希望合成3HP的途径，其中三条途径，包括已发现的最短途径，都是新的。我们还发现了28种商业上可用的化合物的生物合成的新方法，这些化合物目前完全通过有机合成来生产。对这28种化合物在大肠杆菌中生物合成的最佳途径的研究表明，丙酮酸和琥珀酸是从葡萄糖获得高产品产量的理想中间体。生物技术。比昂斯。(C)2010年；106：462-473,2010年威利期刊公司。
Sustainable microbial production of high-value organic compounds such as 3-hydroxypropanoate (3HP) is becoming an increasingly attractive alternative to organic syntheses that utilize petrochemical feedstocks. We applied the Biochemical Network Integrated Computational Explorer (BNICE) framework to the automated design and evaluation of novel biosynthetic routes for the production of 3HP from pyruvate. Among the pathways generated by the BNICE framework were all of the known pathways for the production of 3HP as well as numerous novel pathways. The pathways generated by BNICE were ranked based on four criteria: pathway length, thermodynamic feasibility, maximum achievable yield to 3HP from glucose, and maximum achievable activity at which 3HP can be produced. Four pathways emerged from this ranking as the most promising for the biosynthesis of 3HP, and three of these pathways, including the shortest pathways discovered, were novel. We also discovered novel routes for the biosynthesis of 28 commercially available compounds that are currently produced exclusively through organic synthesis. Examination of the optimal pathways for the biosynthesis of these 28 compounds in E. coli revealed pyruvate and succinate to be ideal intermediates for achieving high product yields from glucose. Biotechnol. Bioeng. (C) 2010;106: 462-473, 2010 Wiley Periodicals, Inc.