Wang Yina, Liu Xiaonan, Chen Bihuan, Liu Wei, Guo Zhaokuan, Liu Xiangyu, Zhu Xiaoxi, Liu Jiayu, Zhang Jin, Li Jing, Zhang Lei, Gao Yadi, Zhang Guanghui, Wang Yan, Choudhary M Iqbal, Yang Shengchao, Jiang Huifeng
National and Local Joint Engineering Research Center on Germplasm Innovation and Utilization of Chinese Medicinal Materials in Southwest China, Yunnan Agricultural University, Yunnan, Kunming, 650201, China.
State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan Agricultural University, Yunnan, Kunming, 650201, China.
Synth Syst Biotechnol. 2022 Jun 6;7(3):958-964. doi: 10.1016/j.synbio.2022.05.009. eCollection 2022 Sep.
Scutellarin related drugs have superior therapeutic effects on cerebrovascular and cardiovascular diseases. Here, an optimal biosynthetic pathway for scutellarin was constructed in platform due to its excellent metabolic potential. By integrating multi-copies of core genes from different species, the production of scutellarin was increased from 15.11 mg/L to 94.79 mg/L and the ratio of scutellarin to the main by-product was improved about 110-fold in flask condition. Finally, the production of scutellarin was improved 23-fold and reached to 346 mg/L in fed-batch bioreactor, which was the highest reported titer for production of scutellarin in microbes. Our results represent a solid basis for further production of natural products on unconventional yeasts and have a potential of industrial implementation.
与灯盏花素相关的药物对脑血管和心血管疾病具有卓越的治疗效果。在此，鉴于其出色的代谢潜力，在平台中构建了一条灯盏花素的最佳生物合成途径。通过整合来自不同物种的多个核心基因拷贝，在摇瓶条件下，灯盏花素的产量从15.11毫克/升提高到94.79毫克/升，灯盏花素与主要副产物的比例提高了约110倍。最终，在补料分批生物反应器中，灯盏花素的产量提高了23倍，达到346毫克/升，这是微生物生产灯盏花素报道的最高滴度。我们的结果为在非常规酵母上进一步生产天然产物奠定了坚实基础，并具有工业实施的潜力。
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