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评估浸没共培养的结果:土曲霉在真菌共培养物中产生洛伐他汀和其他次生代谢物。

Evaluating the outcomes of submerged co-cultivation: production of lovastatin and other secondary metabolites by Aspergillus terreus in fungal co-cultures.

机构信息

Faculty of Process and Environmental Engineering, Department of Bioprocess Engineering, Lodz University of Technology, ul. Wolczanska 213, 90-924, Lodz, Poland.

出版信息

Appl Microbiol Biotechnol. 2019 Jul;103(14):5593-5605. doi: 10.1007/s00253-019-09874-0. Epub 2019 May 16.

Abstract

The goal of the study was to compare the production of secondary metabolites by Aspergillus terreus ATCC 20542 under the conditions of submerged mono- and co-cultivation. The suggested experimental scheme encompassed a diverse set of co-culture initiation strategies differing mostly with respect to the development stage of tested fungal strains at the moment of their confrontation. Three species of filamentous fungi exhibiting distinct patterns of morphological evolution under submerged conditions, namely Penicillium rubens, Chaetomium globosum, and Mucor racemosus, were selected as the co-cultivation partners of A. terreus. The choice of the co-cultivated species and the approach of co-culture triggering noticeably influenced the levels of lovastatin (mevinolinic acid), (+)-geodin, asterric acid, and butyrolactone I in the broth. Even though the evaluated co-cultures did not lead to the increased titers of lovastatin relative to standard monocultures, the biosynthesis of the remaining three metabolites was either enhanced or inhibited depending on the experimental variant. The production of butyrolactone I turned out to be particularly affected by the presence of C. globosum. Interestingly, in the A. terreus/C. globosum co-cultures, the decrease of lovastatin concentration was recorded. According to the most probable scenario, lovastatin was in this case converted to monacolin J acid, a polyketide molecule that may be applied as a substrate for the synthesis of statin drugs. The study revealed that the spores of two distinct fungal species, namely A. terreus and C. globosum, co-agglomerate under submerged conditions to form pellets. Finally, the biosynthetic performance of co-cultures involving four fungal species was evaluated.

摘要

本研究的目的是比较 Aspergillus terreus ATCC 20542 在浸没式单培养和共培养条件下次生代谢产物的产生。建议的实验方案涵盖了一系列不同的共培养起始策略,这些策略主要在测试真菌菌株在接触时的发育阶段上有所不同。选择了三种在浸没条件下表现出不同形态进化模式的丝状真菌(Penicillium rubens、Chaetomium globosum 和 Mucor racemosus)作为 A. terreus 的共培养伙伴。共培养物种的选择和共培养触发方法显著影响了肉汤中 lovastatin(mevinolinic acid)、(+)-geodin、asterric acid 和 butyrolactone I 的水平。尽管评估的共培养并没有导致 lovastatin 的产量相对于标准单培养增加,但其余三种代谢物的生物合成根据实验变体要么增强要么抑制。butyrolactone I 的生产受到 C. globosum 的存在的特别影响。有趣的是,在 A. terreus/C. globosum 共培养中,观察到 lovastatin 浓度降低。根据最可能的情况,lovastatin 在这种情况下被转化为 monacolin J 酸,这是一种多酮分子,可作为合成他汀类药物的底物。研究表明,两种不同真菌物种的孢子,即 A. terreus 和 C. globosum,在浸没条件下共同聚集形成颗粒。最后,评估了涉及四种真菌物种的共培养的生物合成性能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf60/6597594/bd5df1ceef18/253_2019_9874_Fig1_HTML.jpg

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