Shen Xiaolin, Wang Jia, Gall Bradley K, Ferreira Eric M, Yuan Qipeng, Yan Yajun
Beijing Advanced Innovation Center for Soft Matter Science and Engineering , Beijing University of Chemical Technology , Beijing 100029 , China.
State Key Laboratory of Chemical Resource Engineering , Beijing University of Chemical Technology , Beijing 100029 , China.
ACS Synth Biol. 2018 Apr 20;7(4):1012-1017. doi: 10.1021/acssynbio.8b00051. Epub 2018 Mar 29.
Salicyl alcohol and gentisyl alcohol are two important phenolic alcohols that possess significant biological activities and pharmaceutical properties. Here, we report establishment of novel biosynthetic pathways for microbial production of salicyl alcohol and gentisyl alcohol from renewable feedstocks. We first examined the promiscuity of the carboxylic acid reductase CAR toward salicylic acid and 2,5-DHBA, which enabled efficient synthesis of salicyl alcohol and gentisyl alcohol. Then, we employed a novel salicylic acid 5-hydroxylase to achieve 2,5-DHBA production from salicylic acid. After that, the de novo biosynthetic pathways were assembled and optimized by programming the carbon flux into the shikimate pathway. The final titers of salicyl alcohol and gentisyl alcohol reached to 594.4 mg/L and 30.1 mg/L, respectively. To our knowledge, this work achieved microbial production of salicyl alcohol and gentisyl alcohol for the first time. Our present study also demonstrated application of enzyme promiscuity to establish non-natural biosynthetic pathways for the production of high-value compounds.
水杨醇和龙胆醇是两种重要的酚醇，具有显著的生物活性和药用特性。在此，我们报告了从可再生原料出发，通过微生物生产水杨醇和龙胆醇的新型生物合成途径的建立。我们首先研究了羧酸还原酶CAR对水杨酸和2,5-二羟基苯甲酸的底物选择性，这使得能够高效合成水杨醇和龙胆醇。然后，我们使用一种新型的水杨酸5-羟化酶从水杨酸实现2,5-二羟基苯甲酸的生产。之后，通过将碳通量编程进入莽草酸途径来组装和优化从头生物合成途径。水杨醇和龙胆醇的最终产量分别达到594.4毫克/升和30.1毫克/升。据我们所知，这项工作首次实现了微生物生产水杨醇和龙胆醇。我们目前的研究还证明了酶的底物选择性在建立用于生产高价值化合物的非天然生物合成途径中的应用。
