ABSTRACT
A marine-derived actinomycete (Streptomyces sp. MBTI36) exhibiting antibacterial activities was investigated in the present study. The strain was identified using genetic techniques. The 16S rDNA sequence of the isolate indicated that it was most closely related to Streptomyces microflavus. Furthermore, a new chromomycin A9 (1), along with chromomycin Ap (2), chromomycin A2 (3), and chromomycin A3 (4), were isolated from the ethyl acetate extract. Their structures were determined using extensive spectroscopic methods including 1D and 2D NMR, and HRMS, as well as comparisons with previously reported data. Compounds 1-4 showed potent antibacterial activities against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). During a passage experiment, minimum inhibitory concentration (MIC) values for compounds 1-4 showed no more than a 4-fold increase from the starting MIC value, indicating that no resistance was detected over the 21 passages.
Subject(s)
Anti-Bacterial Agents/pharmacology , Chromomycins/pharmacology , Streptomyces/chemistry , Streptomyces/metabolism , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Aquatic Organisms/chemistry , Aquatic Organisms/classification , Aquatic Organisms/genetics , Aquatic Organisms/metabolism , Chromomycins/chemistry , Chromomycins/isolation & purification , Drug Resistance, Bacterial , Gram-Positive Bacteria/drug effects , Microbial Sensitivity Tests , RNA, Ribosomal, 16S/genetics , Streptomyces/classification , Streptomyces/geneticsABSTRACT
Pulvomycins B-D (1-3) were discovered from an estuarine Streptomyces strain along with the known pulvomycin (4). The 22-membered macrocyclic lactone structures of 1-3 were determined based on the interpretation of NMR, UV, and MS data, the modified Mosher's method, and Kishi's bidentate chiral solvent NMR spectroscopy. Genomic analysis of the bacterial strain revealed the biosynthetic gene cluster of pulvomycin and enabled us to propose the trans-acyltransferase polyketide biosynthetic pathway. Pulvomycin D displayed potent cytotoxic activity against various cancer cell lines.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Macrolides/chemistry , Macrolides/metabolism , Streptomyces/metabolism , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Humans , Macrolides/pharmacologyABSTRACT
Twelve new sesterterpenes along with eight known sesterterpenes were isolated from the marine sponge Hyrtios erectus collected off the coast of Chuuk Island, the Federated State of Micronesia. Based upon a combination of spectroscopic and computational analyses, these compounds were determined to be eight glycine-bearing scalaranes (1-8), a 3-keto scalarane (9), two oxidized-furan-bearing scalaranes (10 and 11), and a salmahyrtisane (12). Several of these compounds exhibited weak antiproliferation against diverse cancer cell lines as well as moderate anti-angiogenesis activities. The antiproliferative activity of new compound 4 was found to be associated with G0/G1 arrest in the cell cycle.
