Ambigols from the Cyanobacterium <i>Fischerella ambigua</i> Increase Prodigiosin Production in <i>Serratia</i> spp

When a library of 573 cyanobacteria extracts was screened for inhibition of the quorum sensing regulated prodigiosin production of <i>Serratia marcescens</i>, an extract of the cyanobacterium <i>Fischerella ambigua</i> (Näg.) Gomont 108b was found to drastically increase 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 <i>Serratia</i> sp. ATCC 39006 (S39006) by a factor of 10, while ambigols A and D were found to have antibiotic activity against this strain. The 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 <i>Serratia</i>, as well as increased expression of genes related to the uptake of l-proline. These results suggest that the ambigols increase 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.