Progress and prospect for synthetic biology research of the industrial filamentous fungi Aspergillus terreus

doi:10.12211/2096-8280.2020-002

Abstract

Abstract:

Filamentous fungi are a class of important microorganisms, which have played an important role in the fields of industrial sectors and people's daily life for the production of food, medicine, and chemical products. With the development of synthetic biology, filamentous fungi have shown more potentials. Aspergillus terreus is an industrially valuable filamentous fungus, which has been applied in the production of the bio-based chemical itaconic acid and the lipid-lowering drug lovastatin. The excellent synthetic ability of natural products and outstanding fermentation properties of A. terreus have been fully demonstrated through industrial applications. Meanwhile, it has also been acknowledged that A. terreus would be a promising filamentous fungal chassis cell for synthetic biology development. In recent years, many studies have been performed using A. terreus, including genetic engineering of industrial strains, optimization of fermentation processes, elucidation of biosynthetic mechanisms, etc., which have significantly contributed to the development of A. terreus synthetic biology.

Herewith, these recent research advances are reviewed from: 1) Synthetic biology tools for A. terreus. The development of genetic operation systems is introduced, including the characterization and application of promoters and markers and the progress of gene-editing technologies. 2) Industrial cell factory for the lipid-lowering drug lovastatin. In addition to the biosynthetic pathway of lovastatin, the design and construction of an efficient monacolin J-producing cell factory based on the industrial A. terreus strains are introduced in details. 3) Industrial cell factory for the bio-based chemical itaconic acid. The biosynthetic pathway of itaconic acid and the systematic metabolic engineering of the industrial strain are introduced. 4) Biosynthesis of secondary metabolites. The biosynthetic mechanism and research strategies for the secondary metabolites are introduced. 5) The advantages and prospects of A. terreus chassis cells in synthetic biology are summarized, and the practical applications are listed. Based on the research progress of A. terreus and other filamentous fungi, the challenges and future work of A. terreus biosynthesis technology development are proposed, including enriching the genetic element library, developing efficient gene editing methods and building high-throughput evaluation platforms. Addressing these challenges will provide more alternative design strategies for building more efficient cell factories of A. terreus, and will also contribute to promoting synthetic biology research of filamentous fungi.

Key words: Filamentous fungi, Aspergillus terreus, synthetic biology, cell factory, lovastatin, itaconic acid, biosynthesis of natural products

摘要：

丝状真菌作为一类重要的微生物，在食品、医药、化工等国计民生领域发挥了重要作用，其合成生物技术的发展已经展示了更大的工业应用潜力。土曲霉是一种非常具有工业生产价值的丝状真菌，是生物基化学品衣康酸和降血脂药物洛伐他汀的工业生产菌，展现出了强大的天然产物合成能力和突出的工业发酵性能，具有成为典型性丝状真菌底盘细胞应用于合成生物技术开发的价值。近年来，在土曲霉工业菌株改造与发酵工艺优化、生物合成机制解析等方面都开展了系列的研究，显著推动了其合成生物技术研究的发展。本文综述了土曲霉合成生物技术工具开发、衣康酸和洛伐他汀工业生产菌株改造优化、次级代谢产物生物合成机制解析等方面的最新研究进展，并对土曲霉的合成生物技术应用前景和发展方向进行了展望。挖掘土曲霉底盘细胞在合成生物学研究中的优势，可以更好地拓展合成生物技术的应用。

关键词: 丝状真菌, 土曲霉, 合成生物学, 细胞工厂, 洛伐他汀, 衣康酸, 天然产物生物合成

CLC Number:

Q939.97

Xuenian HUANG, Shen TANG, Xuefeng LV. Progress and prospect for synthetic biology research of the industrial filamentous fungi Aspergillus terreus[J]. Synthetic Biology Journal, 2020, 1(2): 187-211.

黄雪年, 唐慎, 吕雪峰. 工业丝状真菌土曲霉合成生物技术研究进展及展望[J]. 合成生物学, 2020, 1(2): 187-211.

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[3]	Zhonghu BAI, He REN, Jianqi NIE, Yang SUN. The recent progresses and applications of in-parallel fermentation technology [J]. Synthetic Biology Journal, 2023, 4(5): 904-915.
[4]	Yujie WU, Xinxin LIU, Jianhui LIU, Kaiguang Yang, Zhigang SUI, Lihua ZHANG, Yukui ZHANG. Research progress of strain screening and quantitative analysis of key molecules based on high-throughput liquid chromatography and mass spectrometry [J]. Synthetic Biology Journal, 2023, 4(5): 1000-1019.
[5]	Zhehui HU, Juan XU, Guangkai BIAN. Application of automated high-throughput technology in natural product biosynthesis [J]. Synthetic Biology Journal, 2023, 4(5): 932-946.
[6]	Huan LIU, Qiu CUI. Advances and applications of ambient ionization mass spectrometry in screening of microbial strains [J]. Synthetic Biology Journal, 2023, 4(5): 980-999.
[7]	Yannan WANG, Yuhui SUN. Base editing technology and its application in microbial synthetic biology [J]. Synthetic Biology Journal, 2023, 4(4): 720-737.
[8]	Wanqiu LIU, Xiangyang JI, Huiling XU, Yicong LU, Jian LI. Cell-free protein synthesis system enables rapid and efficient biosynthesis of restriction endonucleases [J]. Synthetic Biology Journal, 2023, 4(4): 840-851.
[9]	Meili SUN, Kaifeng WANG, Ran LU, Xiaojun JI. Rewiring and application of Yarrowia lipolytica chassis cell [J]. Synthetic Biology Journal, 2023, 4(4): 779-807.
[10]	Jicong LIN, Gen ZOU, Hongmin LIU, Yongjun WEI. Application of CRISPR/Cas genome editing technology in the synthesis of secondary metabolites of filamentous fungi [J]. Synthetic Biology Journal, 2023, 4(4): 738-755.
[11]	Zhi SUN, Ning YANG, Chunbo LOU, Chao TANG, Xiaojing YANG. Rational design for functional topology and its applications in synthetic biology [J]. Synthetic Biology Journal, 2023, 4(3): 444-463.
[12]	Qilong LAI, Shuai YAO, Yuguo ZHA, Hong BAI, Kang NING. Microbiome-based biosynthetic gene cluster data mining techniques and application potentials [J]. Synthetic Biology Journal, 2023, 4(3): 611-627.
[13]	Qiaozhen MENG, Fei GUO. Applications of foldability in intelligent enzyme engineering and design: take AlphaFold2 for example [J]. Synthetic Biology Journal, 2023, 4(3): 571-589.
[14]	Sheng WANG, Zechen WANG, Weihua CHEN, Ke CHEN, Xiangda PENG, Fafen OU, Liangzhen ZHENG, Jinyuan SUN, Tao SHEN, Guoping ZHAO. Design of synthetic biology components based on artificial intelligence and computational biology [J]. Synthetic Biology Journal, 2023, 4(3): 422-443.
[15]	Hailong LV, Jian WANG, Hao LV, Jin WANG, Yong XU, Dayong GU. Synthetic biology for next-generation genetic diagnostics [J]. Synthetic Biology Journal, 2023, 4(2): 318-332.