title: Significant natural product biosynthetic potential of actinorhizal symbionts of the genus frankia, as revealed by comparative genomic and proteomic analyses.
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.
authors.affiliation: Scripps Institution of Oceanography, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0204, USA. danudwary@mail.uri.edu
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Udwary
authors.forename: Erin A
authors.initials: EA
authors.lastname: Gontang
authors.forename: Adam C
authors.initials: AC
authors.lastname: Jones
authors.forename: Carla S
authors.initials: CS
authors.lastname: Jones
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Schultz
authors.forename: Jaclyn M
authors.initials: JM
authors.lastname: Winter
authors.forename: Jane Y
authors.initials: JY
authors.lastname: Yang
authors.forename: Nicholas
authors.initials: N
authors.lastname: Beauchemin
authors.forename: Todd L
authors.initials: TL
authors.lastname: Capson
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Clark
authors.forename: Eduardo
authors.initials: E
authors.lastname: Esquenazi
authors.forename: Alessandra S
authors.initials: AS
authors.lastname: Eustáquio
authors.forename: Kelle
authors.initials: K
authors.lastname: Freel
authors.forename: Lena
authors.initials: L
authors.lastname: Gerwick
authors.forename: William H
authors.initials: WH
authors.lastname: Gerwick
authors.forename: David
authors.initials: D
authors.lastname: Gonzalez
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Liu
authors.forename: Karla L
authors.initials: KL
authors.lastname: Malloy
authors.forename: Katherine N
authors.initials: KN
authors.lastname: Maloney
authors.forename: Markus
authors.initials: M
authors.lastname: Nett
authors.forename: Joshawna K
authors.initials: JK
authors.lastname: Nunnery
authors.forename: Kevin
authors.initials: K
authors.lastname: Penn
authors.forename: Alejandra
authors.initials: A
authors.lastname: Prieto-Davo
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Simmons
authors.forename: Sara
authors.initials: S
authors.lastname: Weitz
authors.forename: Micheal C
authors.initials: MC
authors.lastname: Wilson
authors.forename: Louis S
authors.initials: LS
authors.lastname: Tisa
authors.forename: Pieter C
authors.initials: PC
authors.lastname: Dorrestein
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Moore
mesh_terms: D001688:Biological Products / Q000096:biosynthesis*; D053898:Biosynthetic Pathways / Q000235:genetics*; D040161:Frankia / Q000235:genetics* / Q000378:metabolism*; D023281:Genomics; D005810:Multigene Family; D040901:Proteomics
chemical_list: D001688:Biological Products