Significant Natural Product Biosynthetic Potential of Actinorhizal Symbionts of the Genus Frankia, as Revealed by Comparative Genomic and Proteomic Analyses

Authors

Daniel W. Udwary, University of Rhode Island
Erin A. Gontang, University of California San Diego
Adam C. Jones, University of California San Diego
Carla S. Jones, University of California San Diego
Andrew W. Schultz, University of California San Diego
Jaclyn M. Winter, University of California San Diego
Jane Y. Yang, University of California San Diego
Nicholas J. Beauchemin, University of New Hampshire, DurhamFollow
Todd L. Capson, University of California San Diego
Benjamin R. Clark, University of California San Diego
Eduardo Esquenazi, University of California San Diego
Alessandra S. Eustaquio, University of California San Diego
Kelle Freel, University of California San Diego
Lena Gerwick, University of California San Diego
William H. Gerwick, University of California San Diego
David Gonzalez, University of California San Diego
Wei-Ting Liu, University of California San Diego
Karla L. Malloy, University of California San Diego
Katherine N. Maloney, University of California San Diego
Markus Nett, University of California San Diego
Joshawna K. Nunnery, University of California San Diego
Kevin Penn, University of California San Diego
Alejandra Prieto-Davo, University of California San Diego
Thomas L. Simmons, University of California San Diego
Sara Weitz, University of California San Diego
Micheal C. Wilson, University of California San Diego
Louis S. Tisa, University of New Hampshire, DurhamFollow
Pieter C. Dorrestein, University of California San Diego
Bradley S. Moore, University of California San Diego

Abstract

Bacteria of the genus Frankia are mycelium-forming actinomycetes that are found as nitrogen-fixing facultative symbionts of actinorhizal plants. Although soil-dwelling actinomycetes are well-known producers of bioactive compounds, the genus Frankia has largely gone uninvestigated for this potential. Bioinformatic analysis of the genome sequences of Frankia strains ACN14a, CcI3, and EAN1pec revealed an unexpected number of secondary metabolic biosynthesis gene clusters. Our analysis led to the identification of at least 65 biosynthetic gene clusters, the vast majority of which appear to be unique and for which products have not been observed or characterized. More than 25 secondary metabolite structures or structure fragments were predicted, and these are expected to include cyclic peptides, siderophores, pigments, signaling molecules, and specialized lipids. Outside the hopanoid gene locus, no cluster could be convincingly demonstrated to be responsible for the few secondary metabolites previously isolated from other Frankia strains. Few clusters were shared among the three species, demonstrating species-specific biosynthetic diversity. Proteomic analysis of Frankia sp. strains CcI3 and EAN1pec showed that significant and diverse secondary metabolic activity was expressed in laboratory cultures. In addition, several prominent signals in the mass range of peptide natural products were observed in Frankia sp. CcI3 by intact-cell matrix-assisted laser desorption-ionization mass spectrometry (MALDI-MS). This work supports the value of bioinformatic investigation in natural products biosynthesis using genomic information and presents a clear roadmap for natural products discovery in the Frankia genus.

Department

Molecular, Cellular and Biomedical Sciences

Publication Date

4-15-2011

Journal Title

Applied and Environmental Microbiology

Publisher

American Society for Microbiology

Digital Object Identifier (DOI)

https://dx.doi.org/10.1128/AEM.00038-11

Document Type

Article

Recommended Citation

Udwary, DW, E. A. Gontang, A. C. Jones, A. W. Schultz, C. M. Sorrels, J. M. Winter, J. Y. Yang, N. Beauchemin, T. L. Capson, B. R. Clark, E. Esquenazi, A. S. Eustáquio, K. Freel, D. J. Gonzalez, L. Gerwick, W. H. Gerwick, W.-T. Liu, K. L. Malloy, K. N. Maloney, M. Nett, J. K. Nunnery, K. Penn, A. Prieto-Davo, T. L. Simmons, S. Weitz, M. C. Wilson, L. S. Tisa, P. C. Dorrestein, and B. S. Moore. 2011. Significant Natural Product Biosynthetic Potential of Actinorhizal Symbionts of the Genus Frankia, as Revealed by Comparative Genomic and Proteomic Analyses. Appl. Environ. Microbiol. 77:3617-3625 (doi:10.1128/AEM.00038-11)

Comments

This is an article published by American Society for Microbiology in Applied and Environmental Microbiology in 2011, available online: https://dx.doi.org/10.1128/AEM.00038-11