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.

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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

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article

Metabolic Blockade-Based Genome Mining of Saccharopolyspora erythraea SCSIO 07745: Discovery and Biosynthetic Pathway of Aminoquinolinone Alkaloids Bearing 6/6/5 Tricyclic and 6/6/6/5 Tetracyclic Scaffolds

Runping Fang, Jianhua Ju, Zhuo Shang, Xiang Weng et al.
3 citations
Organic Letters
Microbial Natural Products and Biosynthesis
1.34
article

Metabolic Blockade-Based Genome Mining of Saccharopolyspora erythraea SCSIO 07745: Discovery and Biosynthetic Pathway of Aminoquinolinone Alkaloids Bearing 6/6/5 Tricyclic and 6/6/6/5 Tetracyclic Scaffolds

Runping Fang, Jianhua Ju, Zhuo Shang, Xiang Weng, Yang Hu, Kunlong Li, Hongjie Zhu, Changli Sun, Junying Ma, Weilong Liu, Pachaiyappan Saravana Kumar, Ge Tian, Xuan Ma
article en
3 citations

Abstract

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.

Organic LettersVol. 27(1)
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)
National Natural Science Foundation of China, Natural Science Foundation of Shandong Province, National Key Research and Development Program of China
Openalex Percentile: Top 17%
Microbial Natural Products and Biosynthesis
1.34
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