Metabolomic Comparison and Assessment of Co-cultivation and a Heat-Killed Inducer Strategy in Activation of Cryptic Biosynthetic Pathways
- Libang Liang
- Guanqiao WangGuanqiao WangDepartment of Chemistry, University of Prince Edward Island, Charlottetown C1A 4P3, CanadaMore by Guanqiao Wang
- Bradley HaltliBradley HaltliDepartments of Biomedical Sciences, University of Prince Edward Island, Charlottetown C1A 4P3, CanadaNautilus Biosciences Croda, Charlottetown C1A 4P3, CanadaMore by Bradley Haltli
- Douglas H. Marchbank
- Henrik StryhnHenrik StryhnHealth Management, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown C1A 4P3, CanadaMore by Henrik Stryhn
- Hebelin CorreaHebelin CorreaNautilus Biosciences Croda, Charlottetown C1A 4P3, CanadaMore by Hebelin Correa
- , and
- Russell G. Kerr*Russell G. Kerr*Tel: (902) 566-0565. Fax: (902) 566-7445. E-mail: [email protected]Department of Chemistry, University of Prince Edward Island, Charlottetown C1A 4P3, CanadaDepartments of Biomedical Sciences, University of Prince Edward Island, Charlottetown C1A 4P3, CanadaNautilus Biosciences Croda, Charlottetown C1A 4P3, CanadaMore by Russell G. Kerr
Co-cultivation has been used as a promising tool to turn on or up-regulate cryptic biosynthetic pathways for microbial natural product discovery. Recently, a modified culturing strategy similar to co-cultivation was investigated, where heat-killed inducer cultures were supplemented to the culture medium of producer fermentations to induce cryptic pathways. In the present study, the repeatability and effectiveness of both methods in turning on cryptic biosynthetic pathways were unbiasedly assessed using UHPLC-HRESIMS-based metabolomics analysis. Both induction methods had good repeatability, and they resulted in very different induced metabolites from the tested producers. Co-cultivation generated more induced mass features than the heat-killed inducer cultures, while both methods resulted in the induction of mass features not observed using the other induction method. As examples, pathways leading to two new natural products, N-carbamoyl-2-hydroxy-3-methoxybenzamide (1) and carbazoquinocin G (5), were induced and up-regulated through co-culturing a producer Streptomyces sp. RKND-216 with inducers Alteromonas sp. RKMC-009 and M. smegmatis ATCC 120515, respectively.
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