Please use this identifier to cite or link to this item: https://ir.swu.ac.th/jspui/handle/123456789/29571
ชื่อเรื่อง: New insights into the neuroprotective and beta-secretase1 inhibitor profiles of tirandamycin B isolated from a newly found Streptomyces composti sp. nov.
ผู้แต่ง: Duangupama T.
Pratuangdejkul J.
Chongruchiroj S.
Pittayakhajonwut P.
Intaraudom C.
Tadtong S.
Nunthanavanit P.
Samee W.
He Y.-W.
Tanasupawat S.
Thawai C.
วันที่เผยแพร่: 2023
สำนักพิมพ์: Nature Research
บทคัดย่อ: Tirandamycin (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 SBST2-5T is a member of the genus Streptomyces and 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 thermoviolaceus NBRC 13905T, values that are significantly below the suggested cut-off values for the species delineation, indicating that strain SBST2-5T could be considered to represent a novel species of the genus Streptomyces. 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 Aβ1–42 administration 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. © 2023, The Author(s).
URI: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85151045098&doi=10.1038%2fs41598-023-32043-3&partnerID=40&md5=fe2837955450692e242b3eedda67be01
https://ir.swu.ac.th/jspui/handle/123456789/29571
Appears in Collections:Scopus 2023

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