Structure-inhibitory activity relationships of pyrrolnitrin analogues on its biosynthesis.
Pyrrolnitrin is a bacterial metabolite, served as a natural lead of agricultural fungicides. In a previous study, fenpiclonil was proven to inhibit the oxidative transformation of aminopyrrolnitrin to pyrrolnitrin, catalyzed by aminopyrrolnitrin oxidase (PrnD). This monooxygenase has an interesting catalytic activity of selective oxidation of aromatic amines, rather than aliphatic amines. However, its structural details are not well understood. In this study, various analogues of pyrrolnitrin were prepared to elucidate the structures of active site of PrnD through structure-activity relationships. In vivo pyrrolnitrin biosynthesis inhibition was determined with Burkholderia sp. O33 and Pseudomonas fluorescens Pf-5. Quantitative analysis of pyrrolnitrin and precursors indicates that 2,3-disubstituted phenyl at 3rd carbon and small substituents at 4th carbon of pyrrole are strictly required to give strong inhibitory effects. In addition, dissociable proton of pyrrole is also critical for inhibitory activity. Molecular simulation with homology-based PrnD model suggests a highly restricted conformational space in active site. The results may help more detailed understanding of this unusual enzyme. In addition, the information will be useful for the development of novel fungicide, compatible with pyrrolnitrin-producing bacterium.
Keum
Young Soo
YS
Department of Molecular Biotechnology, Konkuk University, Gwangjin-gu, Seoul, Republic of Korea. rational@konkuk.ac.kr
Zhu
Yong-Zhe
YZ
Kim
Jeong-Han
JH
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism* / Q000633:toxicity; D053898:Biosynthetic Pathways; D019117:Burkholderia / Q000254:growth & development / Q000378:metabolism; D020134:Catalytic Domain; D010088:Oxidoreductases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D011551:Pseudomonas fluorescens / Q000254:growth & development / Q000378:metabolism; D011764:Pyrrolnitrin / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism* / Q000633:toxicity
D000900:Anti-Bacterial Agents; D010088:Oxidoreductases; D011764:Pyrrolnitrin