Heterologous Production of Lasso Peptide Capistruin in a Burkholderia Host

Burkholderia bacteria are an emerging source of natural products with applications in agriculture and medicine. Heterologous expression of biosynthetic gene clusters can streamline natural product discovery. However, production yields with the commonly used Escherichia coli host are usually low. Following the current paradigm that one host does not fit all, we aim to develop a Burkholderia host in order to ultimately tap into the biosynthetic potential of Burkholderia genomes, which can contain up to 27 biosynthetic gene clusters per genome. Because close phylogenetic relationship is expected to improve odds of success due to compatible gene expression and precursor supply, we tested Burkholderia sp. FERM BP-3421, a non-pathogenic isolate previously used to produce natural products at industrial scale. We show here that FERM BP-3421 can produce the model lasso peptide capistruin in yields that are at least 65-fold, and up to 580-fold higher than the previously used E. coli host.