Project description:Chemical investigation of two cultured cyanobacteria, Westiellopsis sp. (SAG strain number 20.93) and Fischerella muscicola (UTEX strain number LB1829) led to the isolation of three hapalindole-type alkaloids, namely hapalindole X (1), deschloro hapalindole I (2), and 13-hydroxy dechlorofontonamide (3), along with ten known indole alkaloids (hapalindoles A, C, G, H, I, J, and U, hapalonamide H, anhydrohapaloxindole A, and fischerindole L) and fischerellins A and B. The structures were determined by a combination of spectroscopic analyses mainly based on 1D and 2D NMR and HRESIMS data. Selected compounds were evaluated for cytotoxicity and exhibited weak to moderate cytotoxicity against HT-29, MCF-7, NCI-H460, SF268, and IMR90 cells. All compounds, except hapalindole C, were evaluated for 20S proteasome inhibition and displayed either weak or no inhibition at 25 μg/mL. Selected compounds were also evaluated for antimicrobial activity, and hapalindoles X (1) and A, and hapalonamide H showed potent activity against both Mycobacterium tuberculosis and Candida albicans with MIC values ranging from 0.6 to 2.5 μM.
Project description:Screening a library of 573 cyanobacteria extracts for inhibition of the quorum sensing regulated prodigiosin production of Serratia marcescens, an extract of the cyanobacterium Fischerella ambigua (Näg.) Gomont 108b was found to drastically increase the prodigiosin production. Bioactivity-guided isolation of the active compounds resulted in the two new natural products ambigol D and E along with the known ambigols A and C. Ambigol C treatment increased prodiginine production of Serratia sp. ATCC 39006 (S39006) by a factor of 10, while ambigols A and D were found to have antibiotic activity against this strain. RNA-Seq of S39006 treated with ambigol C and subsequent differential gene expression and functional enrichment analyses indicated a significant downregulation of genes associated with the translation machinery and fatty acid biosynthesis in Serratia, as well as increased expression of genes related to the uptake of l-proline. These results suggest that the ambigols increase the prodiginine production in S39006 not by activating the SmaIR quorum sensing system, but possibly by increasing the precursor supply of l-proline and malonyl-CoA.