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

Abstract

Metabolic blockade-based genome mining of the marine sediment-derived Saccharopolyspora erythraea SCSIO 07745 led to the discovery of 11 novel aminoquinolinone alkaloids, oxazoquinolinones A–J (1–10), characterized by an oxazolidone[3,2-α]quinoline-5,8-dione scaffold, and oxazoquinolinone K (11), featuring an unprecedented fused 6/6/6/5 tetracyclic core ring system. Additionally, 5 new biosynthetic intermediates or shunt products (12–16) and a known metabolite sannanine (17) 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 1–17 were proposed. Additionally, oxazoquinolinone K (11) obviously inhibited cell invasion of human glioma cell line LN229 cells at 10 μM.