New strategies and approaches for engineering biosynthetic gene clusters of microbial natural products.
With the rapidly growing number of sequenced microbial (meta)genomes, enormous cryptic natural product (NP) biosynthetic gene clusters (BGCs) have been identified, which are regarded as a rich reservoir for novel drug discovery. A series of powerful tools for engineering BGCs has accelerated the discovery and development of pharmaceutically active NPs. Here, we describe recent advances in the strategies for BGCs manipulation, which are driven by emerging technologies, including efficient DNA recombination systems, versatile CRISPR/Cas9 genome editing tools and diverse DNA assembly methods. We further discuss how these approaches could be used for genome mining studies and industrial strain improvement.
Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China; University of Chinese Academy of Sciences, Beijing 100039, China.
Lei
L
Li
Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China; Jiangsu National Synergetic Innovation Center for Advanced Materials, SICAM, Nanjing 210009, China. Electronic address: whjiang@sibs.ac.cn.
Weihong
W
Jiang
Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China; Shanghai Collaborative Innovation Center for Biomanufacturing Technology, Shanghai 200237, China. Electronic address: yhlu@sibs.ac.cn.
Yinhua
Y
Lu
D001688:Biological Products; D064113:CRISPR-Cas Systems; D004269:DNA, Bacterial / Q000235:genetics*; D004271:DNA, Fungal / Q000235:genetics*; D004274:DNA, Recombinant / Q000235:genetics; D055808:Drug Discovery / Q000379:methods*; D060847:Metabolic Engineering / Q000379:methods*; D054892:Metagenome; D005810:Multigene Family / Q000235:genetics*; D058615:Synthetic Biology / Q000379:methods*
D001688:Biological Products; D004269:DNA, Bacterial; D004271:DNA, Fungal; D004274:DNA, Recombinant
Biosynthetic gene cluster; CRISPR/Cas9; DNA assembly; DNA recombination; Metabolic engineering; Natural product; Synthetic biology