New insights into the neuroprotective and beta-secretase1 inhibitor profiles of tirandamycin B isolated from a newly found Streptomyces composti sp. nov.

Duangupama, Thitikorn; Pratuangdejkul, Jaturong; Chongruchiroj, Sumet; Pittayakhajonwut, Pattama; Intaraudom, Chakapong; Tadtong, Sarin; Nunthanavanit, Patcharawee; Samee, Weerasak; He, Ya Wen; Tanasupawat, Somboon; Thawai, Chitti

doi:10.1038/s41598-023-32043-3

New insights into the neuroprotective and beta-secretase1 inhibitor profiles of tirandamycin B isolated from a newly found Streptomyces composti sp. nov.

Author(s)

Duangupama, Thitikorn

Pratuangdejkul, Jaturong

Chongruchiroj, Sumet

Pittayakhajonwut, Pattama

Intaraudom, Chakapong

Tadtong, Sarin

Nunthanavanit, Patcharawee

Samee, Weerasak

He, Ya Wen

Tanasupawat, Somboon

Thawai, Chitti

Date Issued

December 1, 2023

Type

Article

DOI

10.1038/s41598-023-32043-3

Abstract

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, SBST2-5^T, 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 SBST2-5^T 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 13905^T, values that are significantly below the suggested cut-off values for the species delineation, indicating that strain SBST2-5^T 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.

Citation

Scientific Reports, 13(1), 2023