Abstract
Many novel microbial nature products were discovered from Actinobacteria by genome mining methods. However, only a few number of genome mining works were carried out in rare actinomycetes. An important reason precluding the genome mining efforts in rare actinomycetes is that most of them are recalcitrant to genetic manipulation. Herein, we chose the rare marine actinomycete Streptosporangium sp. CGMCC 4.7309 to explore its secondary metabolite diversity by genome mining. The genetic manipulation method has never been established for Streptosporangium strains. At first, we set up the genetic system of Streptosporangium sp. CGMCC 4.7309 unprecedentedly. The draft genome sequencing of Streptosporangium sp. CGMCC 4.7309 revealed that it contains more than 20 cryptic secondary metabolite biosynthetic clusters. A type II polyketide synthases-containing cluster (the hex cluster) was predicted to encode compounds with a pentangular polyphenol scaffold by in silico analysis. The products of the hex cluster were uncovered by comparing the metabolic profile of Streptosporangium sp. CGMCC 4.7309 with that of the hex30 inactivated mutant, in which a key ketoreductase gene was disrupted. Finally, three pentangular polyphenols were isolated and named as hexaricins A (1), B (2), and C (3). The inconsistency of the stereochemistry of C-15 in hexaricins A, B, and C indicates a branch point in their biosynthesis. Finally, the biosynthetic pathway of the hexaricins was proposed based on bioinformatics analysis.
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Acknowledgments
We thank Dr. Jinwei Ren, Dr. Guomin Ai, and Dr. Wenzhao Wang, Institute of Microbiology, Chinese Academy of Sciences, for MS and NMR data collection. This work was supported in part by the Ministry of Science and Technology of China (2013CB734000, 2015CB150600) and the National Natural Science Foundation of China (31370095 and 31522001). Y.C. is an awardee for the “Hundred Talents Program” of the Chinese Academy of Sciences.
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Jun Tian and Haiyan Chen contributed equally to this work.
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Tian, J., Chen, H., Guo, Z. et al. Discovery of pentangular polyphenols hexaricins A–C from marine Streptosporangium sp. CGMCC 4.7309 by genome mining. Appl Microbiol Biotechnol 100, 4189–4199 (2016). https://doi.org/10.1007/s00253-015-7248-z
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DOI: https://doi.org/10.1007/s00253-015-7248-z