State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, Shanghai 200240, People’s Republic of China; State Key Laboratory of Microbial Technology, Shandong University, Jinan 250100, People's Republic of China.
Sci Rep. 2011;1:142. doi: 10.1038/srep00142. Epub 2011 Nov 4.
Whole cell biocatalysis is an important tool for pharmaceutical intermediates synthesis, although it is hindered by some shortcomings, such as high cost and toxicity of inducer, mass transfer resistance caused by cell membrane and side reactions. Whole-cell catalysis using N-acetyl-d-glucosamine 2-epimerase (EC 5.1.3.8) and N-acetyl-d-neuraminic acid (Neu5Ac) aldolase (EC 4.1.3.3) is a promising approach for the production of Neu5Ac, a potential precursor of many anti-viral drugs. A powerful catalyst was developed by packaging the enzymes in an engineered bacterium and using a safe temperature-induced vector. Since the mass transfer resistance and the side reactions were substantially reduced, a high Neu5Ac amount (191 mM) was achieved. An efficient method was also presented, which allows one-pot synthesis of Neu5Ac with a safe and economic manner. The results highlight the promise of large-scale Neu5Ac synthesis and point at a potential of our approach as a general strategy to improve whole-cell biocatalysis.
全细胞生物催化是一种重要的制药中间体合成工具，尽管它受到一些缺点的阻碍，如诱导剂的高成本和毒性、细胞膜引起的传质阻力和副反应。使用 N-乙酰-d-葡萄糖胺 2-差向异构酶（EC 5.1.3.8）和 N-乙酰-d-神经氨酸（Neu5Ac）醛缩酶（EC 4.1.3.3）的全细胞催化是生产 Neu5Ac 的一种很有前途的方法，Neu5Ac 是许多抗病毒药物的潜在前体。通过将酶包装在工程菌中并使用安全的温度诱导载体，开发了一种强大的催化剂。由于传质阻力和副反应大大降低，因此可以获得大量的 Neu5Ac（191mM）。还提出了一种有效的方法，可安全、经济地一锅法合成 Neu5Ac。这些结果突出了大规模 Neu5Ac 合成的前景，并指出了我们的方法作为一种提高全细胞生物催化的通用策略的潜力。
