Discovery of Ureido-Containing Alteropeptilides and Intramolecular Cyclized Alteramides in Pseudoalteromonas flavipulchra S16 by Promoter Engineering of Cryptic Biosynthetic Gene Clusters

Pseudoalteromonas are abundant in the oceans and possess great potential in the synthesis of bioactive natural products. Although many secondary metabolite biosynthetic gene clusters have been identified from Pseudoalteromonas genomes, most of their products have not been characterized. In this study, endogenous constitutive promoters with high transcriptional activity were obtained from Pseudoalteromonas flavipulchra S16 through RNA-seq and a fluorescence assay of luciferase gene expression. Through in situ promoter replacement two silent biosynthetic gene clusters (BGCs) were successfully activated, leading to production of intramolecular cyclized alteramides and two novel ureido-containing linear peptides, alteropeptilides. This study provides a feasible approach for the activation of silent BGCs and the mining of novel compounds from marine bacteria.