Author:
Duangupama Thitikorn,Pratuangdejkul Jaturong,Chongruchiroj Sumet,Pittayakhajonwut Pattama,Intaraudom Chakapong,Tadtong Sarin,Nunthanavanit Patcharawee,Samee Weerasak,He Ya-Wen,Tanasupawat Somboon,Thawai Chitti
Abstract
AbstractTirandamycin (TAM B) is a tetramic acid antibiotic discovered to be active on a screen designed to find compounds with neuroprotective activity. The producing strain, SBST2-5T, is an actinobacterium that was isolated from wastewater treatment bio–sludge compost collected from Suphanburi province, Thailand. Taxonomic characterization based on a polyphasic approach indicates that strain SBST2-5Tis a member of the genusStreptomycesand shows low average nucleotide identity (ANI) (81.7%), average amino-acid identity (AAI) (78.5%), and digital DNA-DNA hybridization (dDDH) (25.9%) values to its closest relative,Streptomyces thermoviolaceusNBRC 13905T, values that are significantly below the suggested cut-off values for the species delineation, indicating that strain SBST2-5Tcould be considered to represent a novel species of the genusStreptomyces. The analysis of secondary metabolites biosynthetic gene clusters (smBGCs) in its genome and chemical investigation led to the isolation of TAM B. Interestingly, TAM B at 20 µg/mL displayed a suppressive effect on beta-secretase 1 (BACE1) with 68.69 ± 8.84% inhibition. Molecular docking simulation reveals the interaction mechanism between TAM B and BACE1 that TAM B was buried in the pocket of BACE-1 by interacting with amino acids Thr231, Asp 228, Gln73, Lys 107 via hydrogen bond and Leu30, Tyr71, Phe108, Ile118 via hydrophobic interaction, indicating that TAM B represents a potential active BACE1 inhibitor. Moreover, TAM B can protect the neuron cells significantly (% neuron viability = 83.10 ± 9.83% and 112.72 ± 6.83%) from oxidative stress induced by serum deprivation and Aβ1–42administration models at 1 ng/mL, respectively, without neurotoxicity on murine P19-derived neuron cells nor cytotoxicity against Vero cells. This study was reportedly the first study to show the neuroprotective and BACE1 inhibitory activities of TAM B.
Funder
The School of Science, King Mongkut’s Institute of Technology Ladkrabang
Publisher
Springer Science and Business Media LLC
Reference90 articles.
1. Puksasook, T. et al. Semisynthesis and biological evaluation of prenylated resveratrol derivatives as multi-targeted agents for Alzheimer’s disease. J. Nat. Med. 71, 665–682 (2017).
2. Panyatip, P., Tadtong, S., Sousa, E. & Puthongking, P. BACE1 inhibitor, neuroprotective, and neuritogenic activities of melatonin derivatives. Sci. Pharm. 88, 58 (2020).
3. Jiaranaikulwanitch, J. et al. Novel multi-functional ascorbic triazole derivatives for amyloidogenic pathway inhibition, anti-inflammation, and neuroprotection. Molecules 26, 1562 (2021).
4. Bérdy, J. Bioactive microbial metabolites. J. Antibiot. 58, 1–26 (2005).
5. Kämpfer, P. Genus Streptomyces. In Bergey’s Manual of Systematic Bacteriology 2nd edn, Vol. 4 (eds Goodfellow, M. et al.) 1455–1767 (Springer, 2012).