Genomatica, Inc., San Diego, California, USA.
Nat Chem Biol. 2011 May 22;7(7):445-52. doi: 10.1038/nchembio.580.
1,4-Butanediol (BDO) is an important commodity chemical used to manufacture over 2.5 million tons annually of valuable polymers, and it is currently produced exclusively through feedstocks derived from oil and natural gas. Herein we report what are to our knowledge the first direct biocatalytic routes to BDO from renewable carbohydrate feedstocks, leading to a strain of Escherichia coli capable of producing 18 g l(-1) of this highly reduced, non-natural chemical. A pathway-identification algorithm elucidated multiple pathways for the biosynthesis of BDO from common metabolic intermediates. Guided by a genome-scale metabolic model, we engineered the E. coli host to enhance anaerobic operation of the oxidative tricarboxylic acid cycle, thereby generating reducing power to drive the BDO pathway. The organism produced BDO from glucose, xylose, sucrose and biomass-derived mixed sugar streams. This work demonstrates a systems-based metabolic engineering approach to strain design and development that can enable new bioprocesses for commodity chemicals that are not naturally produced by living cells.
1,4-丁二醇（BDO）是一种重要的大宗商品化学品，每年用于制造超过 250 万吨有价值的聚合物，目前仅通过源自石油和天然气的原料生产。在此，我们报告了从可再生碳水化合物原料到 BDO 的首个直接生物催化途径，这导致了能够生产 18 克/升这种高度还原的非天然化学物质的大肠杆菌菌株。途径鉴定算法阐明了 BDO 从常见代谢中间产物生物合成的多种途径。在基因组规模代谢模型的指导下，我们对大肠杆菌宿主进行了工程改造，以增强氧化三羧酸循环的厌氧操作，从而产生还原力以驱动 BDO 途径。该生物从葡萄糖、木糖、蔗糖和生物质衍生的混合糖流中生产 BDO。这项工作展示了一种基于系统的代谢工程菌株设计和开发方法，可用于开发并非由活细胞自然产生的大宗商品化学品的新工艺。
