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Engineering carotenoid production in mammalian cells for nutritionally enhanced cell-cultured foods.
Metabolic Engineering ( IF 8.4 ) Pub Date : 2020-09-02 , DOI: 10.1016/j.ymben.2020.07.011
Andrew J Stout 1 , Addison B Mirliani 1 , Erin L Soule-Albridge 1 , Julian M Cohen 2 , David L Kaplan 1
Affiliation  

Metabolic engineering of mammalian cells has to-date focused primarily on biopharmaceutical protein production or the manipulation of native metabolic processes towards therapeutic aims. However, significant potential exists for expanding these techniques to diverse applications by looking across the taxonomic tree to bioactive metabolites not synthesized in animals. Namely, cross-taxa metabolic engineering of mammalian cells could offer value in applications ranging fromfood and nutrition to regenerative medicine and gene therapy. Towards the former, recent advances in meat production through cell culture suggest the potential to produce meat with fine cellular control, where tuning composition through cross-taxa metabolic engineering could enhance nutrition and food-functionality. Here we demonstrate this possibility by engineering primary bovine and immortalized murine muscle cells with prokaryotic enzymes to endogenously produce the antioxidant carotenoids phytoene, lycopene and β-carotene. These phytonutrients offer general nutritive value and protective effects against diseases associated with red and processed meat consumption, and so offer a promising proof-of-concept for nutritional engineering in cultured meat. We demonstrate the phenotypic integrity of engineered cells, the ability to tune carotenoid yields, and the antioxidant functionality of these compounds in vitro towards both nutrition and food-quality objectives. Our results demonstrate the potential for tailoring the nutritional profile of cultured meats. They further lay a foundation for heterologous metabolic engineering of mammalian cells for applications outside of the clinical realm.



中文翻译:

在哺乳动物细胞中工程化类胡萝卜素的生产,以增强细胞培养食品的营养。

迄今为止,哺乳动物细胞的代谢工程主要集中于生物制药蛋白质的生产或操纵天然代谢过程以实现治疗目的。然而,通过跨越分类树寻找动物体内未合成的生物活性代谢物,将这些技术扩展到不同的应用方面存在巨大的潜力。也就是说,哺乳动物细胞的跨类群代谢工程可以在从食品和营养到再生医学和基因治疗的应用中提供价值。对于前者,通过细胞培养进行肉类生产的最新进展表明,通过精细细胞控制生产肉类的潜力,其中通过跨类群代谢工程调整成分可以增强营养和食品功能。在这里,我们通过用原核酶改造原代牛和永生化小鼠肌肉细胞来内源性产生抗氧化剂类胡萝卜素八氢番茄红素、番茄红素和β-胡萝卜素,证明了这种可能性。这些植物营养素具有一般的营养价值,并对与食用红肉和加工肉类相关的疾病具有保护作用,因此为培养肉的营养工程提供了有前景的概念验证。我们展示了工程细胞的表型完整性、调节类胡萝卜素产量的能力以及这些化合物在体外的抗氧化功能,以实现营养和食品质量目标。我们的结果证明了调整培养肉营养成分的潜力。他们进一步为哺乳动物细胞的异源代谢工程在临床领域之外的应用奠定了基础。

更新日期:2020-09-02
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