Lycopene over-accumulation by disruption of the negative regulator gene crgA in Mucor circinelloides

Lycopene over-accumulation by disruption of the negative regulator gene crgA in Mucor circinelloides
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DOI:
10.1007/s00253-007-1281-5
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发表时间:
2008-02-01
影响因子:
5
通讯作者:
Ruiz-Vazquez, Rosa M.
Ruiz-Vazquez, Rosa M.
中科院分区:
工程技术2区
文献类型:
--
作者:
Nicolas-Molina, Francisco E.;Navarro, Eusebio;Ruiz-Vazquez, Rosa M.

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番茄红素已成为最有趣的抗氧化剂化合物之一,特别是与人类健康相关。这项工作描述了一种修改类胡萝卜素生物合成途径以开发番茄红素过量生产菌株的遗传策略。 crgA 基因是胡萝卜素生成的负调节因子,在卷枝毛霉菌株 MU202 中被破坏,该菌株缺乏番茄红素环化酶活性并积累番茄红素而不是 β-胡萝卜素。与亲本菌株 MU202 相比,所得菌株 MU224 表现出胡萝卜素生成结构基因 carRP 和 carB 的转录水平增加。结果,菌株 MU224 在液体培养物中积累了 5 mg/g 的细胞干重,相对于亲本菌株增加了七倍。此外,当在复杂的富集培养基中检查番茄红素的产生时,生物量比合成基本培养基中获得的生物量增加了十倍。在该复合培养基中,菌株MU224的番茄红素生产率达到54g/1。这些结果说明了如何利用基因操作和优化培养条件的组合来提高商业上所需的化合物(例如番茄红素)的产量。
Lycopene has become one of the most interesting antioxidant compounds, especially in relation to human health. This work describes a genetic strategy to modify the carotenoid biosynthesis pathway to develop a lycopene-overproducing strain. The crgA gene, a negative regulator of carotenogenesis, was disrupted in the Mucor circinelloides strain MU202, which lacks the lycopene cyclase activity and accumulates lycopene instead of beta-carotene. The resultant strain, MU224, demonstrated increased transcriptional levels of the carotenogenesis structural genes carRP and carB compared to the parental strain MU202. As a consequence, strain MU224 accumulated 5 mg/g of dry weight of cells in liquid cultures, a sevenfold increase with respect to the parental strain. Moreover, when lycopene production was examined in a complex enriched medium, biomass increased tenfold compared to that obtained in synthetic minimal medium. In this complex medium, the production rate of lycopene by strain MU224 reached 54 g/1. These results illustrate how a combination of genetic manipulation and optimized culture conditions can be utilized to enhance the production of commercially desirable compounds such as lycopene.