Metabolic Blockade-Based Genome Mining of <i>Saccharopolyspora erythraea</i> SCSIO 07745: Discovery and Biosynthetic Pathway of Aminoquinolinone Alkaloids Bearing 6/6/5 Tricyclic and 6/6/6/5 Tetracyclic Scaffolds
Metabolic blockade-based genome mining of the marine sediment-derived <i>Saccharopolyspora erythraea</i> SCSIO 07745 led to the discovery of 11 novel aminoquinolinone alkaloids, oxazoquinolinones A-J (<b>1</b>-<b>10</b>), characterized by an oxazolidone[3,2-α]quinoline-5,8-dione scaffold, and oxazoquinolinone K (<b>11</b>), featuring an unprecedented fused 6/6/6/5 tetracyclic core ring system. Additionally, 5 new biosynthetic intermediates or shunt products (<b>12</b>-<b>16</b>) and a known metabolite sannanine (<b>17</b>) were identified. Their structures were elucidated by extensive spectroscopic analyses and a comparison of electronic circular dichroism and single-crystal X-ray diffraction. On the basis of the functional gene analyses and structures of the intermediates or shunt products, plausible biosynthetic pathways for compounds <b>1</b>-<b>17</b> were proposed. Additionally, oxazoquinolinone K (<b>11</b>) obviously inhibited cell invasion of human glioma cell line LN229 cells at 10 μM.
Authors
- Runping Fang (ORCID: https://orcid.org/0000-0002-7443-7155)
- Jianhua Ju (ORCID: https://orcid.org/0000-0001-7712-8027)
- Zhuo Shang (ORCID: https://orcid.org/0000-0002-5755-2629)
- Xiang Weng
- Yang Hu (ORCID: https://orcid.org/0000-0002-9646-5755)
- Kunlong Li (ORCID: https://orcid.org/0000-0002-1474-3097)
- Hongjie Zhu (ORCID: https://orcid.org/0000-0002-2604-033X)
- Changli Sun
- Junying Ma (ORCID: https://orcid.org/0000-0002-0641-7291)
- Weilong Liu (ORCID: https://orcid.org/0000-0002-5084-3466)
- Pachaiyappan Saravana Kumar (ORCID: https://orcid.org/0000-0003-1988-6414)
- Ge Tian (ORCID: https://orcid.org/0000-0003-2707-4723)
- Xuan Ma
Institutions
- Shandong University (CN)
- Chinese Academy of Sciences (CN)
- Institute of Oceanology (CN)
- South China Sea Institute Of Oceanology (CN)
- University of Chinese Academy of Sciences (CN)
Publication Details
- Journal
- Organic Letters
- Published
- 2024-12-20
- DOI
- https://doi.org/10.1021/acs.orglett.4c04491
- Citations
- 3
- Primary Topic
- Microbial Natural Products and Biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 1.34
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Shandong Province
- National Key Research and Development Program of China