Recent progress of synthetic biology applications in microbial pharmaceuticals research

doi:10.12211/2096-8280.2020-036

Abstract

Abstract:

Microbial natural products are a major source in the innovation of novel pharmaceuticals, including anti-bacterial, anti-tumor, and immunosuppressive agents for clinical use. Currently, the development of microbial drugs is facing significant challenges due to the growing prevalence of multidrug-resistant bacteria, the continuous emergence of new pathogens and viruses, and the increasing difficulties in the discovery of natural products with new scaffolds. Synthetic biology is an emerging interdisciplinary research area leading to great breakthrough in the field of biomedical sciences in the 21st century, which provides new methods and ideas for drug discovery and development. The application of synthetic biology could unlock the potential of natural product mining, design new biosynthetic routes, and generate much more “unnatural” natural products and structural analogs. This review summarizes the technical innovations of synthetic biology in the field of microbial pharmaceuticals, and its applications in the mining, biosynthesis, and new scaffold generation of aminoglycoside antibiotics, nucleotide antibiotics, ribosomally synthesized and posttranslationally modified peptides, terpenoids, and polyketides in the last five years.

Key words: natural products, synthetic biology, microbial pharmaceuticals, biosynthesis, dark matter

摘要：

微生物天然产物一直都是新型生物药物创新的主要源泉，是目前开发临床抗菌、抗肿瘤、免疫抑制剂等药物的重要资源。随着临床耐药菌的日益增多，新型病原菌和病毒的不断出现，以及新骨架天然产物挖掘难度的增加，新型微生物药物的开发正面临着巨大挑战。作为21世纪生命医学领域催动原创突破和学科交叉融合的前沿学科，合成生物学的崛起为解决药物研发困境提供了新的思路和方法，它可以突破天然药物发现的瓶颈，设计新的生物合成途径，产生更多天然药物及类似物。本文综述了近五年来合成生物学在微生物药物研究领域的技术革新，及其在氨基糖苷类抗生素、核苷类抗生素、核糖体肽、萜类以及聚酮类化合物等5大类微生物天然药物的发掘、生物合成以及新结构创制等方面的应用。

关键词: 天然产物, 合成生物学, 微生物药物, 生物合成, 暗物质

CLC Number:

Cong RAO, Xuan YUN, Yi YU, Zixin DENG. Recent progress of synthetic biology applications in microbial pharmaceuticals research[J]. Synthetic Biology Journal, 2020, 1(1): 92-102.

饶聪, 云轩, 虞沂, 邓子新. 微生物药物的合成生物学研究进展[J]. 合成生物学, 2020, 1(1): 92-102.

Figures/Tables 4

Fig. 1 The natural multistep biosynthetic pathway of valienamine, and the simplified biosynthetic pathway after modification

Fig. 2 Targeted genome mining of purine nucleoside antibiotics

Fig. 3 The engineered strain SL3052 fed with quinolinic acid and its analogues, leading to the production of siomycin and its analogues

Fig. 4 The synthesis pathway of terpenoids in Saccharomyces cerevisiae

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