오동찬 (서울대학교 약학대학)

한빛사논문

조회303

서울대학교 약학대학

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Angew. Chem.-Int. Edit., Mar 14 2024, | https://doi.org/10.1002/anie.202402465 Discovery of Terminal Oxazole-Bearing Natural Products by a Targeted Metabologenomic Approach

Jiyoon Park,^[a,+] Yern-Hyerk Shin,^[a,+] Sunghoon Hwang,^[a,+] Jungwoo Kim,^[a] Dong Hyun Moon,^[a] Ilnam Kang,^[b] Yoon-Joo Ko,^[c] Beomkoo Chung,^[d] Hyungsung Nam,^[e]Seokhee Kim,^[e] Kyuho Moon,^[f] Ki-Bong Oh^,[d] Jang-Cheon Cho,^[b]Sang Kook Lee,^[a] and Dong-Chan Oh^*[a]

^[a]J. Park,[+]Dr. Y.-H. Shin,[+] Dr. S. Hwang,[+] J. Kim, D. H. Moon, Prof. S. K. Lee, Prof. D.-C. Oh

Natural Products Research Institute, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826 (Republic of Korea)

^[b]Dr. I. Kang, Prof. J.-C. Cho

Departmentof Biological Sciences, Inha University, 100 Inha-ro, Michuhol-gu, Incheon 22212 (Republic of Korea)

^[c]Dr. Y.-J. Ko

Laboratory of Nuclear Magnetic Resonance, National Center for Inter-University Research Facilities (NCIRF), Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826 (Republic of Korea)

^[d]Dr. B. Chung, Prof. K.-B. Oh

Department of Agricultural Biotechnology, College of Agriculture and Life Sciences and Natural Products Research Institute, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826 (Republic of Korea)

^[e]Dr. H. Nam, Prof. S. Kim

Department of Chemistry, College of Natural Sciences, and Natural Products Research Institute, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826 (Republic of Korea)

^[f]College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447(Republic of Korea)

^[+]These authors contributed equally to this work.

^*CORRESPONDING AUTHOR : Dong-Chan Oh

Abstract

A targeted metabologenomic method was developed to selectively discover terminal oxazole-bearing natural products from bacteria. For this, genes encoding oxazole cyclase, a key enzyme in terminal oxazole biosynthesis, were chosen as the genomic signature to screen bacterial strains that may produce oxazole-bearing compounds. Sixteen strains were identified from the screening of a bacterial DNA library (1,000 strains) using oxazole cyclase gene-targeting polymerase chain reaction (PCR) primers. The PCR amplicon sequences were subjected to phylogenetic analysis and classified into nine clades. 1H-13C coupled-HSQC NMR spectra obtained from the culture extracts of the hit strains enabled the unequivocal detection of the target compounds, including five new oxazole compounds, based on the unique 1JCH values and chemical shifts of oxazole: lenzioxazole (1) possessing an unprecedented cyclopentane, permafroxazole (2) bearing a tetraene conjugated with carboxylic acid, tenebriazine (3) incorporating two modified amino acids, and methyl-oxazolomycins A and B (4 and 5). Tenebriazine displayed inhibitory activity against pathogenic fungi, whereas methyl-oxazolomycins A and B (4 and 5) selectively showed anti-proliferative activity against estrogen receptor-positive breast cancer cells. This metabologenomic method enables the logical and efficient discovery of new natural microbial products with a target structural motif without the need for isotopic labeling.

논문정보

형식Research article
게재일2024년 03월 (BRIC 등록일 2024-03-27)
연구진국내 연구진
분야 의약학 > 약학

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