Multiplexed mobilization and expression of biosynthetic gene clusters

Vincent Libis, Logan W. MacIntyre, Rabia Mehmood, Liliana Guerrero, Melinda A. Ternei, Niv Antonovsky, Ján Burian, Zongqiang Wang and Sean F. Brady ()
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Vincent Libis: The Rockefeller University
Logan W. MacIntyre: The Rockefeller University
Rabia Mehmood: The Rockefeller University
Liliana Guerrero: The Rockefeller University
Melinda A. Ternei: The Rockefeller University
Niv Antonovsky: The Rockefeller University
Ján Burian: The Rockefeller University
Zongqiang Wang: The Rockefeller University
Sean F. Brady: The Rockefeller University

Nature Communications, 2022, vol. 13, issue 1, 1-10

Abstract: Abstract Bacterial genomes contain large reservoirs of biosynthetic gene clusters (BGCs) that are predicted to encode unexplored natural products. Heterologous expression of previously unstudied BGCs should facilitate the discovery of additional therapeutically relevant bioactive molecules from bacterial culture collections, but the large-scale manipulation of BGCs remains cumbersome. Here, we describe a method to parallelize the identification, mobilization and heterologous expression of BGCs. Our solution simultaneously captures large numbers of BGCs by cloning the genomes of a strain collection in a large-insert library and uses the CONKAT-seq (co-occurrence network analysis of targeted sequences) sequencing pipeline to efficiently localize clones carrying intact BGCs which represent candidates for heterologous expression. Our discovery of several natural products, including an antibiotic that is active against multi-drug resistant Staphylococcus aureus, demonstrates the potential of leveraging economies of scale with this approach to systematically interrogate cryptic BGCs contained in strain collections.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32858-0

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DOI: 10.1038/s41467-022-32858-0

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