改造马疫链球菌兽疫亚种,使其同时生产具有生物医学价值的透明质酸和硫酸软骨素生物聚合物。
Engineering S. equi subsp. zooepidemicus towards concurrent production of hyaluronic acid and chondroitin biopolymers of biomedical interest.
作者信息
Cimini Donatella, Iacono Ileana Dello, Carlino Elisabetta, Finamore Rosario, Restaino Odile F, Diana Paola, Bedini Emiliano, Schiraldi Chiara
机构信息
Department of Experimental Medicine, University of Campania Luigi Vanvitelli (ex Second University of Naples), via de Crecchio 7, 80138, Naples, Italy.
Department of Chemical Sciences, University of Naples "Federico II", Complesso Universitario Monte S. Angelo, via Cinthia, 4, 80126, Naples, Italy.
出版信息
AMB Express. 2017 Dec;7(1):61. doi: 10.1186/s13568-017-0364-7. Epub 2017 Mar 14.
Glycosaminoglycans, such as hyaluronic acid and chondroitin sulphate, are not only more and more required as main ingredients in cosmeceutical and nutraceutical preparations, but also as active principles in medical devices and pharmaceutical products. However, while biotechnological production of hyaluronic acid is industrially established through fermentation of Streptococcus spp. and recently Bacillus subtilis, biotechnological chondroitin is not yet on the market. A non-hemolytic and hyaluronidase negative S. equi subsp. zooepidemicus mutant strain was engineered in this work by the addition of two E. coli K4 genes, namely kfoA and kfoC, involved in the biosynthesis of chondroitin-like polysaccharide. Chondroitin is the precursor of chondroitin sulphate, a nutraceutical present on the market as anti-arthritic drug, that is lately being studied for its intrinsic bioactivity. In small scale bioreactor batch experiments the production of about 1.46 ± 0.38 g/L hyaluronic acid and 300 ± 28 mg/L of chondroitin with an average molecular weight of 1750 and 25 kDa, respectively, was demonstrated, providing an approach to the concurrent production of both biopolymers in a single fermentation.
糖胺聚糖,如透明质酸和硫酸软骨素,不仅越来越多地被用作药妆品和营养保健品制剂的主要成分,还被用作医疗器械和药品中的活性成分。然而,虽然透明质酸的生物技术生产已通过链球菌属的发酵在工业上得以确立,最近枯草芽孢杆菌也可用于此,但是生物技术生产的软骨素尚未上市。在本研究中,通过添加两个参与类软骨素多糖生物合成的大肠杆菌K4基因,即kfoA和kfoC,构建了一种非溶血性且透明质酸酶阴性的马链球菌兽疫亚种突变菌株。软骨素是硫酸软骨素的前体,硫酸软骨素作为一种抗关节炎药物在市场上作为营养保健品出售,最近其内在生物活性正受到研究。在小规模生物反应器分批实验中,证明分别产生了约1.46±0.38 g/L的透明质酸和300±28 mg/L的软骨素,其平均分子量分别为1750和25 kDa,这为在单一发酵中同时生产这两种生物聚合物提供了一种方法。
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