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

in Organic letters by Kunlong Li, Hongjie Zhu, Changli Sun, Ge Tian, Xuan Ma, Pachaiyappan Saravana Kumar, Xiang Weng, Hu Yang, Runping Fang, Weilong Liu, Zhuo Shang, Junying Ma, Jianhua Ju

TLDR

  • This study discovered 11 novel aminoquinolinone alkaloids and several biosynthetic intermediates from marine sediment-derived SCSIO 07745, providing insights into their structures, biosynthetic pathways, and potential biological activities.

Abstract

Metabolic blockade-based genome mining of the marine sediment-derivedSCSIO 07745 led to the discovery of 11 novel aminoquinolinone alkaloids, oxazoquinolinones A-J (-), characterized by an oxazolidone[3,2-α]quinoline-5,8-dione scaffold, and oxazoquinolinone K (), featuring an unprecedented fused 6/6/6/5 tetracyclic core ring system. Additionally, 5 new biosynthetic intermediates or shunt products (-) and a known metabolite sannanine () 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-were proposed. Additionally, oxazoquinolinone K () obviously inhibited cell invasion of human glioma cell line LN229 cells at 10 μM.

Overview

  • The study aimed to discover novel aminoquinolinone alkaloids from marine sediment-derived SCSIO 07745 using metabolic blockade-based genome mining.
  • The study identified 11 novel compounds with an oxazolidone[3,2-α]quinoline-5,8-dione scaffold, as well as 5 biosynthetic intermediates, and a known metabolite.
  • The objective was to uncover the structures, biosynthetic pathways, and potential biological activities of these newly discovered compounds.

Comparative Analysis & Findings

  • The study elucidated the structures of the novel compounds using spectroscopic analyses and single-crystal X-ray diffraction.
  • The study proposed plausible biosynthetic pathways for the identified compounds based on functional gene analyses and structures of intermediates.
  • Oxazoquinolinone K was found to inhibit cell invasion of human glioma cell line LN229 cells at 10 μM.

Implications and Future Directions

  • The study's findings have implications for the development of new bioactive compounds with potential therapeutic applications.
  • Future studies can aim to further characterize the biological activities and potentiation mechanisms of the discovered compounds.
  • The study's methodology and discoveries can also be applied to the discovery of new metabolites from marine-derived organisms.
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