Discovery of\nUreido-Containing Alteropeptilides and\nIntramolecular Cyclized Alteramides in <i>Pseudoalteromonas flavipulchra</i> S16 by Promoter Engineering of Cryptic Biosynthetic Gene Clusters

<i>Pseudoalteromonas</i> are abundant in the\noceans and\npossess great potential in the synthesis of bioactive natural products.\nAlthough many secondary metabolite biosynthetic gene clusters have\nbeen identified from <i>Pseudoalteromonas</i> genomes, most\nof their products have not been characterized. In this study, endogenous\nconstitutive promoters with high transcriptional activity were obtained\nfrom <i>Pseudoalteromonas flavipulchra</i> S16 through RNA-seq\nand a fluorescence assay of luciferase gene expression. Through <i>in situ</i> promoter replacement two silent biosynthetic gene\nclusters (BGCs) were successfully activated, leading to production\nof intramolecular cyclized alteramides and two novel ureido-containing\nlinear peptides, alteropeptilides. This study provides a feasible\napproach for the activation of silent BGCs and the mining of novel\ncompounds from marine bacteria.