{"title":"优化唇形茶孢子菌的生物转化过程,提高强效端粒酶激活剂的产量","authors":"Melis Küçüksolak, Hasan Buğra Çoban, Erdal Bedir","doi":"10.1186/s12934-024-02468-0","DOIUrl":null,"url":null,"abstract":"Telomerase activators are promising agents for the healthy aging process and the treatment/prevention of short telomere-related and age-related diseases. The discovery of new telomerase activators and later optimizing their activities through chemical and biological transformations are crucial for the pharmaceutical sector. In our previous studies, several potent telomerase activators were discovered via fungal biotransformation, which in turn necessitated optimization of their production. It is practical to improve the production processes by implementing the design of experiment (DoE) strategy, leading to increased yield and productivity. In this study, we focused on optimizing biotransformation conditions utilizing Camarosporium laburnicola, a recently discovered filamentous fungus, to afford the target telomerase activators (E-CG-01, E-AG-01, and E-AG-02). DoE approaches were used to optimize the microbial biotransformation processes of C. laburnicola. Nine parameters were screened by Plackett-Burman Design, and three significant parameters (biotransformation time, temperature, shaking speed) were optimized using Central Composite Design. After conducting validation experiments, we were able to further enhance the production yield of target metabolites through scale-up studies in shake flasks (55.3-fold for E-AG-01, 13-fold for E-AG-02, and 1.96-fold for E-CG-01). Following a process optimization study using C. laburnicola, a significant increase was achieved in the production yields. Thus, the present study demonstrates a promising methodology to increase the production yield of potent telomerase activators. Furthermore, C. laburnicola is identified as a potential biocatalyst for further industrial utilization.","PeriodicalId":18582,"journal":{"name":"Microbial Cell Factories","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Optimization of biotransformation processes of Camarosporium laburnicola to improve production yields of potent telomerase activators\",\"authors\":\"Melis Küçüksolak, Hasan Buğra Çoban, Erdal Bedir\",\"doi\":\"10.1186/s12934-024-02468-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Telomerase activators are promising agents for the healthy aging process and the treatment/prevention of short telomere-related and age-related diseases. 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引用次数: 0
摘要
端粒酶激活剂是促进健康老化过程、治疗/预防端粒短相关疾病和老年相关疾病的有效药物。发现新的端粒酶激活剂并通过化学和生物转化优化其活性对制药行业至关重要。在我们之前的研究中,通过真菌生物转化发现了几种有效的端粒酶激活剂,这反过来又需要优化它们的生产。通过实施实验设计(DoE)策略来改进生产工艺,从而提高产量和生产率是切实可行的。在本研究中,我们重点利用最近发现的丝状真菌--拉布尼柯拉樟孢菌(Camarosporium laburnicola)优化生物转化条件,以获得目标端粒酶激活剂(E-CG-01、E-AG-01 和 E-AG-02)。采用 DoE 方法优化了 C. laburnicola 的微生物生物转化过程。通过普拉克特-伯曼设计(Plackett-Burman Design)筛选了九个参数,并利用中央综合设计(Central Composite Design)优化了三个重要参数(生物转化时间、温度、振荡速度)。在进行验证实验后,我们通过摇瓶放大研究进一步提高了目标代谢物的产量(E-AG-01 为 55.3 倍,E-AG-02 为 13 倍,E-CG-01 为 1.96 倍)。在使用 C. laburnicola 进行工艺优化研究后,产量有了显著提高。因此,本研究展示了一种提高强效端粒酶激活剂产量的可行方法。此外,C. laburnicola 被确定为一种可进一步用于工业的潜在生物催化剂。
Optimization of biotransformation processes of Camarosporium laburnicola to improve production yields of potent telomerase activators
Telomerase activators are promising agents for the healthy aging process and the treatment/prevention of short telomere-related and age-related diseases. The discovery of new telomerase activators and later optimizing their activities through chemical and biological transformations are crucial for the pharmaceutical sector. In our previous studies, several potent telomerase activators were discovered via fungal biotransformation, which in turn necessitated optimization of their production. It is practical to improve the production processes by implementing the design of experiment (DoE) strategy, leading to increased yield and productivity. In this study, we focused on optimizing biotransformation conditions utilizing Camarosporium laburnicola, a recently discovered filamentous fungus, to afford the target telomerase activators (E-CG-01, E-AG-01, and E-AG-02). DoE approaches were used to optimize the microbial biotransformation processes of C. laburnicola. Nine parameters were screened by Plackett-Burman Design, and three significant parameters (biotransformation time, temperature, shaking speed) were optimized using Central Composite Design. After conducting validation experiments, we were able to further enhance the production yield of target metabolites through scale-up studies in shake flasks (55.3-fold for E-AG-01, 13-fold for E-AG-02, and 1.96-fold for E-CG-01). Following a process optimization study using C. laburnicola, a significant increase was achieved in the production yields. Thus, the present study demonstrates a promising methodology to increase the production yield of potent telomerase activators. Furthermore, C. laburnicola is identified as a potential biocatalyst for further industrial utilization.
期刊介绍:
Microbial Cell Factories is an open access peer-reviewed journal that covers any topic related to the development, use and investigation of microbial cells as producers of recombinant proteins and natural products, or as catalyzers of biological transformations of industrial interest. Microbial Cell Factories is the world leading, primary research journal fully focusing on Applied Microbiology.
The journal is divided into the following editorial sections:
-Metabolic engineering
-Synthetic biology
-Whole-cell biocatalysis
-Microbial regulations
-Recombinant protein production/bioprocessing
-Production of natural compounds
-Systems biology of cell factories
-Microbial production processes
-Cell-free systems