ACS Synth Biol 2020 Jan 13. Epub 2020 Jan 13.
Department of Pharmaceutical Sciences and Center for Biomolecular Sciences, College of Pharmacy , University of Illinois at Chicago , Chicago , Illinois 60607 , United States.
bacteria are an emerging source of natural products with applications in agriculture and medicine. The heterologous expression of biosynthetic gene clusters can streamline natural product discovery; however, production yields with the commonly used host are usually low. Following the current paradigm that one host does not fit all, we aim to develop a host to ultimately tap into the biosynthetic potential of genomes, which can contain up to 27 biosynthetic gene clusters per genome. Because a close phylogenetic relationship is expected to improve the odds of success due to compatible gene expression and precursor supply, we tested sp. FERM BP-3421, a nonpathogenic isolate previously used to produce natural products at industrial scales. We show here that FERM BP-3421 can produce the model lasso peptide capistruin in yields that are at least 65 times and up to 580 times higher than the previously used host.