Department of Medicinal Chemistry, Center for Natural Products, Drug Discovery and Development, University of Florida, Gainesville, FL 31610, USA.
J Ind Microbiol Biotechnol. 2021 Jun 4;48(3-4). doi: 10.1093/jimb/kuab003.
Cyanobacteria produce a plethora of compounds with unique chemical structures and diverse biological activities. Importantly, the increasing availability of cyanobacterial genome sequences and the rapid development of bioinformatics tools have unraveled the tremendous potential of cyanobacteria in producing new natural products. However, the discovery of these compounds based on cyanobacterial genomes has progressed slowly as the majority of their corresponding biosynthetic gene clusters (BGCs) are silent. In addition, cyanobacterial strains are often slow-growing, difficult for genetic engineering, or cannot be cultivated yet, limiting the use of host genetic engineering approaches for discovery. On the other hand, genetically tractable hosts such as Escherichia coli, Actinobacteria, and yeast have been developed for the heterologous expression of cyanobacterial BGCs. More recently, there have been increased interests in developing model cyanobacterial strains as heterologous production platforms. Herein, we present recent advances in the heterologous production of cyanobacterial compounds in both cyanobacterial and noncyanobacterial hosts. Emerging strategies for BGC assembly, host engineering, and optimization of BGC expression are included for fostering the broader applications of synthetic biology tools in the discovery of new cyanobacterial natural products.
蓝细菌产生大量具有独特化学结构和多种生物活性的化合物。重要的是，随着蓝细菌基因组序列的日益丰富和生物信息学工具的快速发展，蓝细菌在产生新天然产物方面的巨大潜力已经被揭示出来。然而，基于蓝细菌基因组发现这些化合物的进展缓慢，因为它们大多数对应的生物合成基因簇（BGCs）是沉默的。此外，蓝细菌菌株通常生长缓慢，遗传工程困难，或者尚未被培养，这限制了宿主遗传工程方法在发现中的应用。另一方面，已经开发出了可遗传操作的宿主，如大肠杆菌、放线菌和酵母，用于蓝细菌 BGC 的异源表达。最近，人们越来越关注开发模式蓝细菌菌株作为异源生产平台。本文介绍了在蓝细菌和非蓝细菌宿主中异源生产蓝细菌化合物的最新进展。包括 BGC 组装、宿主工程和 BGC 表达优化的新兴策略，以促进合成生物学工具在发现新蓝细菌天然产物方面的更广泛应用。
