Nah Hee-Ju, Pyeon Hye-Rim, Kang Seung-Hoon, Choi Si-Sun, Kim Eung-Soo
Department of Biological Engineering, Inha University Incheon, South Korea.
Front Microbiol. 2017 Mar 15;8:394. doi: 10.3389/fmicb.2017.00394. eCollection 2017.
Actinomycetes family including species have been a major source for the discovery of novel natural products (NPs) in the last several decades thanks to their structural novelty, diversity and complexity. Moreover, recent genome mining approach has provided an attractive tool to screen potentially valuable NP biosynthetic gene clusters (BGCs) present in the actinomycetes genomes. Since many of these NP BGCs are silent or cryptic in the original actinomycetes, various techniques have been employed to activate these NP BGCs. Heterologous expression of BGCs has become a useful strategy to produce, reactivate, improve, and modify the pathways of NPs present at minute quantities in the original actinomycetes isolates. However, cloning and efficient overexpression of an entire NP BGC, often as large as over 100 kb, remain challenging due to the ineffectiveness of current genetic systems in manipulating large NP BGCs. This mini review describes examples of actinomycetes NP production through BGC heterologous expression systems as well as recent strategies specialized for the large-sized NP BGCs in heterologous hosts.
在过去几十年里，放线菌家族的物种一直是发现新型天然产物（NPs）的主要来源，这得益于其结构的新颖性、多样性和复杂性。此外，最近的基因组挖掘方法提供了一种有吸引力的工具，用于筛选放线菌基因组中潜在有价值的NP生物合成基因簇（BGCs）。由于这些NP BGCs中的许多在原始放线菌中是沉默或隐秘的，因此已采用各种技术来激活这些NP BGCs。BGCs的异源表达已成为一种有用的策略，用于生产、重新激活、改进和修饰原始放线菌分离物中少量存在的NP途径。然而，由于当前遗传系统在操纵大型NP BGCs方面效率低下，克隆和高效过表达通常超过100 kb的整个NP BGC仍然具有挑战性。本综述介绍了通过BGC异源表达系统生产放线菌NP的实例，以及在异源宿主中专门针对大型NP BGCs的最新策略。
