The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kemitorvet Building 220, 2800 Kgs, Lyngby, Denmark.
Cysbio ApS, Agern Allé 1, 2970, Hørsholm, Denmark.
Nat Commun. 2019 Sep 6;10(1):4071. doi: 10.1038/s41467-019-12022-x.
Biological production and application of a range of organic compounds is hindered by their limited solubility and toxicity. This work describes a process for functionalization of phenolic compounds that increases solubility and decreases toxicity. We achieve this by screening a wide range of sulfotransferases for their activity towards a range of compounds, including the antioxidant resveratrol. We demonstrate how to engineer cell factories for efficiently creating sulfate esters of phenolic compounds through the use of sulfotransferases and by optimization of sulfate uptake and sulfate nucleotide pathways leading to the 3'-phosphoadenosine 5'-phosphosulfate precursor (PAPS). As an example we produce the antifouling agent zosteric acid, which is the sulfate ester of p-coumaric acid, reaching a titer of 5 g L in fed-batch fermentation. The described approach enables production of sulfate esters that are expected to provide new properties and functionalities to a wide range of application areas.
一系列有机化合物的生物生产和应用受到其有限的溶解度和毒性的限制。本工作描述了一种酚类化合物的功能化方法，该方法提高了溶解度并降低了毒性。我们通过筛选广泛的磺基转移酶来实现这一点，以评估它们对一系列化合物（包括抗氧化剂白藜芦醇）的活性。我们展示了如何通过使用磺基转移酶和优化硫酸盐摄取和硫酸盐核苷酸途径来构建细胞工厂，从而有效地生成酚类化合物的硫酸盐酯，最终生成 3'-磷酸腺苷 5'-磷酸硫酸前体（PAPS）。作为一个例子，我们生产了防污剂褐藻酸，它是对香豆酸的硫酸盐酯，在分批补料发酵中达到了 5g/L 的滴度。所描述的方法能够生产预期为广泛应用领域提供新性能和功能的硫酸盐酯。
