Studies On The Secondary Metabolites From Three Actinomycetes Strains

The mutants of three marine-derived actinomycetes LZ35, LC6, QH12 with the potential of producing ansamycins, and one fungal strain Trichoderma reesei were chemically investigated. A total of 56 compounds including 37 new ones were isolated by column chromatography on silica gel, RP-18, Sephadex LH-20 and HPLC. The structures of these molecules were determined on the basis of UV, IR, MS, NMR and X-ray single crystal diffraction.Strain LZ35 was isolated from intertidal soil collected at Jimei, Xiamen. Previously, hygrocins, elaiophylins, nigericins and geldanamycins have been systematic isolated as the major components from strain LZ35 in our laboratory. Since these major components hampered the isolation of minor compounds, the mutant strain LZ35 △HENG was constructed to provide a raletively clean background.17 compounds including 11 new hybrid isoprenoids quinolinecarboxamides A-E (1-11); 2 new glycosylation of fatty acid derivatives,35D1-2 (12-13); 1 new large ring lactone, meridamycins 35A (14) were obtained from the oatmeal medium of mutant LZ35△HENG.16 compounds including 13 novel benzenic ansamycins, seco-nam I-IV (18-30); 1 new large ring lactone, galbonolides LZ-3 (33) were isolated from the oatmeal medium of mutant LZ35 △HENG△nas-Mo+nas-luxR.3 novel compounds haoxinamides A-C (34-36) generated by NRPS-PKS combination pathway were obtained from the cultivation of mutant LZ35 △8.The strain LC6 was isolated from the leaves of Kandelia candel (Linn.) Druce collected from Longhai, Zhangzhou, Fujian Province. Strain LC6 was predicted to produce novel pentaketide ansamycins by analysis of the putative ansamycin gene cluster in it.12 compounds including 2 novel dimeric pentaketide ansamycins, juanlimycins A-B (37-38); 1 new monomeric pentaketide ansamycins, LC-13; and 1 new 2-aminobenzoic acid substituted by a mycarose, LC-6 were isolated from the cultivation of mutant LC6+Pentaketide-SARP1.1 new compound derivate from polyketide pathway, QZ-2 were obtained from the cultivation of mutant LZ35△6::ER1-7H7.The strain QH12 was isolated from spike rhizospherethe soil collected at Ledu County, Qinghai Province. Strain QH12 was predicted to produce heptaketide ansamycins by analysis of the putative ansamycin gene cluster in it.4 compounds including 1 new o-hydroxy cinnamic acid derivatives, QH-3c (48); 1 new spiro indole alkaloids compound QH-4 (49) were obtained from the cultivation of mutant QH12+ansa-LuxR.The antimicrobial and antitumor activity of several compounds was assayed by paper disk method and SRB method, respectively. The results showed that compound seco-nam IE displayed strong cytotoxicities against colorectal carcinoma cell line SW480 (IC50=9.5μM). In addition, compounds seco-nam Ⅰ (18),Ⅲ(20), Ⅵ(21) and IFa (28) showed strong inhibition on the secretion of SPI-1 effectors (SipA/B/C/D). Among that the seco-nams IFa (28) at concentrations of 25μM still displayed strong inhibitory activity as the positive control Csn-B.