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促进红曲提取物发酵中莫纳可林 K 的生产:真菌形态和生物合成基因簇表达水平的变化。

Promotion of monacolin K production in Monascus extractive fermentation: the variation in fungal morphology and in the expression levels of biosynthetic gene clusters.

机构信息

Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology & Business University (BTBU), Beijing, 100048, China.

Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology & Business University (BTBU), Beijing, 100048, China.

出版信息

J Sci Food Agric. 2021 Oct;101(13):5652-5659. doi: 10.1002/jsfa.11218. Epub 2021 Mar 31.

Abstract

BACKGROUND

Monacolin K, an important secondary metabolite of Monascus, possesses a cholesterol-lowering effect and is widely used in the manufacture of antihypertensive drugs. In the present study, we constructed an extractive fermentation system by adding non-ionic surfactant and acquired a high monacolin K yield. The mechanism was determined by examining both cell morphology and the transcription levels of the related mokA-I genes in the monacolin K biosynthetic gene cluster.

RESULTS

The monacolin K yield was effectively increased to 539.59 mg L during extraction, which was an increase of 386.16% compared to that in the control group fermentation. The non-ionic surfactant showed good biocompatibility with Monascus. Electron scanning microscopy revealed alterations in the morphology of Monascus. The loosened mycelial structure and increased number of cell surface wrinkles were found to be related to the increased cell-membrane permeability and extracellular accumulation of monacolin K. Gene expression levels were measured via a quantitative reverse transciptase-polymerase chain reaction. By contrast, in the control group, mokA, mokB, mokC, mokD and mokF showed higher-level and longer-term expression in the extractive fermentation group, whereas mokE and mokG did not present a similar trend. The expression levels of mokH and mokI, encoding a transcription factor and efflux pump, respectively, were also higher than the control levels.

CONCLUSION

The addition of a non-ionic surfactant to Monascus fermentation effectively increases the yield of monacolin K by transforming the fungus morphology and promoting the expression of monacolin K biosynthesis genes. © 2021 Society of Chemical Industry.

摘要

背景

莫纳可林 K 是红曲霉的一种重要次级代谢产物,具有降胆固醇作用,被广泛应用于降压药的生产。本研究通过添加非离子表面活性剂构建了萃取发酵体系,获得了较高的莫纳可林 K 产量。通过考察莫纳可林 K 生物合成基因簇中相关 mokA-I 基因的细胞形态和转录水平,确定了其机制。

结果

在提取过程中,莫纳可林 K 的产量有效提高到 539.59mg/L,比对照组发酵提高了 386.16%。非离子表面活性剂对红曲霉具有良好的生物相容性。电子扫描显微镜显示红曲霉的形态发生了变化。疏松的菌丝体结构和增加的细胞表面褶皱数量与细胞膜通透性的增加和莫纳可林 K 的细胞外积累有关。通过定量逆转录聚合酶链反应测量基因表达水平。相比之下,在对照组中,在萃取发酵组中,mokA、mokB、mokC、mokD 和 mokF 呈现更高水平和更长时间的表达,而 mokE 和 mokG 则没有呈现出类似的趋势。编码转录因子和外排泵的 mokH 和 mokI 的表达水平也高于对照水平。

结论

向红曲霉发酵液中添加非离子表面活性剂可通过改变真菌形态和促进莫纳可林 K 生物合成基因的表达,有效提高莫纳可林 K 的产量。 © 2021 化学工业协会。

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