Pentaminomycins C–E: Cyclic Pentapeptides as Autophagy Inducers from a Mealworm Beetle Gut Bacterium

Microorganisms

MinJae Lee¹  LyThi Huong Luu Le¹  Jongheon Shin²  Sunghoon Hwang²  Dong-Chan Oh²  Shin-Il Jo³ 

[1] Department of Biochemistry and Molecular Biology, College of Medicine, Seoul National University, Seoul 03080, Korea;Natural Products Research Institute, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea;Welfare Division, Seoul Zoo, Seoul Grand Park, Gwacheon, Gyeonggi 13829, Korea;

关键词: insect;    mealworm;    gut bacteria;    OSMAC;    cyclic peptides;    biosynthetic pathway;   

DOI  :  10.3390/microorganisms8091390

来源: DOAJ

【 摘 要 】

Pentaminomycins C–E (1–3) were isolated from the culture of the Streptomyces sp. GG23 strain from the guts of the mealworm beetle, Tenebrio molitor. The structures of the pentaminomycins were determined to be cyclic pentapeptides containing a modified amino acid, N⁵-hydroxyarginine, based on 1D and 2D NMR and mass spectroscopic analyses. The absolute configurations of the amino acid residues were assigned using Marfey’s method and bioinformatics analysis of their nonribosomal peptide biosynthetic gene cluster (BGC). Detailed analysis of the BGC enabled us to propose that the structural variations in 1–3 originate from the low specificity of the adenylation domain in the nonribosomal peptide synthetase (NRPS) module 1, and indicate that macrocyclization can be catalyzed noncanonically by penicillin binding protein (PBP)-type TE. Furthermore, pentaminomycins C and D (1 and 2) showed significant autophagy-inducing activities and were cytoprotective against oxidative stress in vitro.

【 授权许可】

Unknown