Enzymology and Fungal Biotechnology Lab, Botany and Microbiology Department, Faculty of Science, Zagazig University, Zagazig 44519, Egypt.
Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.
Molecules. 2022 May 9;27(9):3033. doi: 10.3390/molecules27093033.
Exploring the metabolic potency of fungi as camptothecin producers raises the hope of their usage as an industrial source of camptothecin, due to their short-life span and the feasibility of metabolic engineering. However, the tiny yield and loss of camptothecin productivity of fungi during storage and sub-culturing are challenges that counteract this approach. Marine fungi could be a novel source for camptothecin production, with higher yield and reliable metabolic sustainability. The marine fungal isolate EFBL # OL597937.1 derived from the sponge " sp." has been morphologically identified and molecularly confirmed, based on the Internal Transcribed Spacer sequence, exhibiting the highest yield of camptothecin (110 μg/L). The molecular structure and chemical identity of derived camptothecin has been resolved by HPLC, FTIR and LC-MS/MS analyses, giving the same spectroscopic profiles and mass fragmentation patterns as authentic camptothecin. The extracted camptothecin displayed a strong anti-proliferative activity towards HEP-2 and HCT-116 (IC values 0.33-0.35 µM). The yield of camptothecin was maximized by nutritional optimization of with a Plackett-Burman design, and the productivity of camptothecin increased by 1.8 fold (200 µg/L), compared to control fungal cultures. Upon storage at 4 °C as slope culture for 8 months, the productivity of camptothecin for was reduced by 40% compared to the initial culture. Visual fading of the mycelial pigmentation of was observed during fungal storage, matched with loss of camptothecin productivity. Methylene chloride extracts of sp. had the potency to completely restore the camptothecin productivity of , ensuring the partial dependence of the expression of the camptothecin biosynthetic machinery of on the chemical signals derived from the sponge, or the associated microbial flora. This is the first report describing the feasibility of , endozoic of sp., for camptothecin production, along with reliable metabolic biosynthetic stability, which could be a new platform for scaling-up camptothecin production.
探索真菌作为喜树碱产生菌的代谢能力，为其作为喜树碱的工业来源带来了希望，因为真菌的寿命短，且代谢工程具有可行性。然而，真菌在储存和传代过程中喜树碱产量小且生产力丧失，这给这种方法带来了挑战。海洋真菌可能是喜树碱生产的新来源，具有更高的产量和可靠的代谢可持续性。从海绵“sp.”中分离出的海洋真菌菌株 EFBL # OL597937.1，通过内转录间隔区序列进行了形态学鉴定和分子鉴定，其喜树碱产量最高（110 μg/L）。通过 HPLC、FTIR 和 LC-MS/MS 分析确定了衍生喜树碱的分子结构和化学特性，其具有与天然喜树碱相同的光谱特征和质谱裂解模式。提取的喜树碱对 HEP-2 和 HCT-116 具有很强的抗增殖活性（IC 值为 0.33-0.35 μM）。通过 Plackett-Burman 设计对 进行营养优化，使喜树碱的产量最大化，与对照真菌培养物相比，喜树碱的产量增加了 1.8 倍（200 μg/L）。在 4°C 作为斜面对 进行储存 8 个月后，与初始培养物相比， 的喜树碱产量降低了 40%。在真菌储存过程中观察到 的菌丝体色素沉着的视觉褪色，与喜树碱生产力的丧失相匹配。海绵 sp. 的二氯甲烷提取物具有完全恢复 的喜树碱生产力的能力，这确保了 的喜树碱生物合成机制的表达部分依赖于海绵衍生的化学信号或相关的微生物菌群。这是第一个描述 ，sp. 的内生真菌，用于喜树碱生产的可行性，以及可靠的代谢生物合成稳定性的报告，这可能是喜树碱生产扩大规模的新平台。
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Zotero 插件
