Abstract 2255 Burkholderiales bacteria genome mining and heterologous host development

Secondary metabolites (natural products) are an important source of new drugs. However, rediscovery and supply issues hinder their development. A continued understanding of natural product biosynthesis coupled with genomic and synthetic biology approaches promise to revolutionize natural products research. To avoid rediscovery, we focus on underexplored bacterial taxa because it has been predicted that about ¾ of genome-encoded natural products are unique to each bacterial phylum (1). We then employ synthetic biology approaches to improve production. In this presentation, I will discuss our recent efforts towards exploring Burkholderia bacteria as an emerging source of natural products (2, 3), including the development of a Burkholderia host (4, 5) to facilitate natural product discovery from a Burkholderiales strain collection. References 1. Gavriilidou A, Kautsar SA, Zaburannyi N, Krug D, Müller R, Medema MH, Ziemert N (2022) Compendium of specialized metabolite biosynthetic diversity encoded in bacterial genomes. Nat Microbiol 7: 726-735. 2. Kunakom S, Eustáquio AS (2019) Burkholderia as a source of natural products. J Nat Prod 82: 2018-2037. 3. Adaikpoh BI, Fernandez HN, Eustáquio AS (2022) Biotechnology approaches for natural product discovery, engineering, and production based on Burkholderia bacteria. Curr Opin Biotechnol 77:102782. 4. Kunakom S, Eustáquio AS (2020) Heterologous production of lasso peptide capistruin in a Burkholderia host. ACS Synth Biol 9: 241-248. 5. Romanowski SB, Lee S, Kunakom S, Paulo BS, Recchia MJJ, Liu DY, Cavanagh H, Linington RG, Eustáquio AS (2023) Identification of the lipodepsipeptide selethramide encoded in a giant nonribosomal peptide synthetase from a Burkholderia bacterium. Proc Natl Acad Sci U S A 120: e2304668120. Financial support for this work was provided by the National Institute of General Medical Sciences (GM129344).