Studies On The Secondary Metabolites From Five Halophilic Actinomycete Strains

Five halophilic actinomycete strains were selected from a collection of environemtal microorganisms on the baisi of the analysis of gene clusters, metabolites diversity, and biological activity, named Nocardiopsis lucentensis DSM 44048, Saccharopolyspora sp. YIM M13568, Nocardiopsis chromatogenes YIM 90109, Saccharopolyspora sp. YIM M13001 and Nocardiopsis sp. YIM M13066. This study reported the isolation, structure elucidation and bioactivity evaluation of the secondary metabolites of these five halophilic actinomycete strains. In total,48 compounds including 23 new ones were obtained by column chromatography over Sephadex LH-20 and normal phase silica gel, MPLC over reversed-phase RP-18 silica gel, and HPLC. Their structures were determined on the basis of the analysis of MS, NMR, UV, IR, and X-ray single crystal diffractions. Their antimicrobial activity, cytotoxic activity and effect on the Salmonella T3SS were evaluated.The strain N. lucentensis DSM 44048, purchased from the DSM Microbial Type Culture Collection, was cultured on agar medium in petri dishes. Through the isolation and purification, seven benzoxazoles named Nocarbenzoxazoles A-G (1-7), two polyketides named Lucentides A and B (8-9), one dipeptide 048-12 (10), three indole derivatives 048-1,048-8 and 048-5 (11-13), and one 16-membered ring macrolide 048-6 (14) were elucidated. The antimicrobial activity of Nocarbenzoxazoles A-G and Lucentides A-B, and the cytotoxic activity of Nocarbenzoxazoles A-G were evaluated. Nocarbenzoxazole G showed selective activity against human cancer cell lines HepG2 and HeLa.The strain S. sp. YIM M13568 was isolated from the mangrove rhizosphere samples collected in Wenchang County, Hainan Province, China. Through isolation and purification, four quinoline alkaloids Q1-Q4 (15-18), one naphthalene derivative Q5 (19), three erythromycin derivatives 13568-1,13568-6 and 13568-5 (20-22), and one sesquiterpenes 13568-4 (23) were elucidated. The antimicrobial and cytotoxic activity of four quinoline alkaloids Q1-Q4 and one naphthalene derivative Q5 were evaluated.The strain N. chromatogenes YIM 90109 was isolated from the saline soil samples collected in Xinjiang Province, China. Through isolation and purification, three sesquiterpenoids 90109-1,90109A and 90109D (24-26), and one furan derivative 90109-2 (27) were elucidated. The antimicrobial activity, cytotoxic activity and the effect on the secretion of SPI-1 effectors of the three sesquiterpenoids 90109-1,90109A and 90109D were evaluated.The strain N. sp. YIM M13066 was isolated from the deep sea soil samples (109°53.171',16°3.576',-880 m). Through the isolation and purification, seven diketopiperazine derivatives 066F,066C,13066M5,13066M4,13066K2,13066K1 and 13066D (28-34), one phenazine derivative 066G (42), one indole derivative 13066P (36), five ?-pyrones 13066E,13066H,13066F,13066J and 13066-3 (37-41), one aniline derivative 066G (42), and one pyrrole derivative 066N (43) were elucidated. The antimicrobial and antitumor activity of the five new compounds including two new diketopiperazine derivatives 066F and 066C, and three new a-pyrones alkaloids 13066E,13066F and 13066J were evaluated.The strain S. sp.YIM M13001 was isolated from the deep sea soil samples of South China Sea. Through the isolation and purification, two 14-membered macrolides 001-MS-3 and 001-MS-1 (44-45), one benzofuran derivative 13001-1 (46), one phenol derivative 13001-2 (47), and one indole derivative 13001-3 (48) were elucidated.