Salternbromines A and B, Genome Mining-Driven Discovery of Dibrominated Compounds from a Saltern-Derived Streptomyces sp. : Isolation, Structural Elucidation, and Proposed Biosynthetic Pathway of Novel Metabolites from Streptomyces sp. AYP39 = Salternbromines A and B, 염전 유래 방선균 Streptomyces로부터 게놈 마이닝 기반 이중 브롬화 화합물의 발굴

다국어 초록 (Multilingual Abstract)

Brominated metabolites from bacterial sources remain significantly underexplored in natural product research, even in Streptomyces despite their vast biosynthetic potential. In this study, an integrated strategy combining flavin-dependent halogenase (FDH)-targeted genome mining with MS-based metabolomic validation was applied to discover novel brominated natural products. Streptomyces sp. AYP39, isolated from a solar saltern in Incheon, Republic of Korea, was found to produce two new dibrominated phenolics, salternbromines A (1) and B (2), along with two known compounds, 2-methoxy-p- coumaric acid (3) and N-acetyl-3-bromo-4-hydroxylphenylethamine (4). The structures of 1 and 2 were elucidated by comprehensive 1D and 2D NMR, mass spectrometry, and UV analysis as (Z)-3,5-dibromo-2-methoxy-p-coumaric acid (1) and its methyl ester (2), both possessing a 3,5-dibromo-4-hydroxyphenyl core. Genome sequencing and molecular networking revealed five additional putative derivatives and enabled the proposal of two FDH-mediated biosynthetic pathways from L-tyrosine, where FDH Ayp14 catalyzes bromination. Halogen supplementation studies further revealed iodination capability, a rare halogenation in bacterial halogenases. This study demonstrates the efficiency of integrated genome mining for discovering novel halogenated natural products from underexplored bacterial sources.

목차 (Table of Contents)

• Abstract v
• List of Contents vi
• List of Tables vii
• List of Figures viii
• List of Abbreviations x
• Introduction 11
• Experimental Section 15
• Results and Discussion 28
• References 43
• Supplementary Materials 48
• 국문초록 96