An Integrated Metabolomic and Genomic Mining Workflow To Uncover the Biosynthetic Potential of Bacteria

Maansson, Maria; Vynne, Nikolaj Grønnegaard; Klitgaard, Andreas; Nybo, Jane L.; Melchiorsen, Jette; Nguyen, Don D.; Sanchez, Laura M.; Ziemert, Nadine; Dorrestein, Pieter C.; Andersen, Mikael Rørdam; Gram, Lone

doi:10.1128/msystems.00028-15

Cited by 63 publications

(53 citation statements)

References 84 publications

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“…Not all bacteria are equally proficient in secondary metabolite production, and whereas some groups appear to produce few or no metabolites, others such as filamentous soil bacteria and marine vibrios, roseobacters and Pseudoalteromonas spp. produce an array of different bioactive compounds (Brinkhoff et al, 2004;Murphy et al, 2012;Rasmussen et al, 2014;Maansson et al, 2016;Sonnenschein et al, 2017b). Hence, if the role of these compounds is to eliminate competing microorganisms, proficient secondary metabolite producers should be strong drivers of microbial community composition in natural environments.…”

Section: Introductionmentioning

confidence: 99%

Impact of Phaeobacter inhibens on marine eukaryote‐associated microbial communities

Dittmann

Sonnenschein

Egan

et al. 2018

Environ Microbiol Rep

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Summary Bacteria–host interactions are universal in nature and have significant effects on host functionality. Bacterial secondary metabolites are believed to play key roles in such interactions as well as in interactions within the host‐associated microbial community. Hence, prominent secondary metabolite‐producing bacteria may be strong drivers of microbial community composition in natural host‐associated microbiomes. This has, however, not been rigorously tested, and the purpose of this study was to investigate how the secondary metabolite producer Phaeobacter inhibens affects the diversity and composition of microbiomes associated with the microalga Emiliania huxleyi and the European flat oyster, Ostrea edulis. Roseobacters were indigenous to both communities exhibiting relative abundances between 2.8% and 7.0%. Addition of P. inhibens caused substantial changes in the overall structure of the low‐complexity microbiome of E. huxleyi, but did not shape microbial community structure to the same degree in the more complex oyster microbiomes. Species‐specific interactions occurred in both microbiomes and specifically the abundances of other putative secondary metabolite‐producers such as vibrios and pseudoalteromonads were reduced. Thus, the impact of a bioactive strain like P. inhibens on host‐associated microbiomes depends on the complexity and composition of the existing microbiome.

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Section: Introductionmentioning

confidence: 99%

Impact of Phaeobacter inhibens on marine eukaryote‐associated microbial communities

Dittmann

Sonnenschein

Egan

et al. 2018

Environ Microbiol Rep

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“…This population level approach shows that the P. fluorescens population in a single field is highly complex, heterogeneous and dynamic (Figures 2, 3 and 8). The genetic and metabolic diversity of various genera or species groups have previously been investigated in detail for several bacteria, including Salinospora (86), Rhodococcus (87) and Pseudoalteromonas (88), Burkholderia (89) as well as prior studies on P. fluorescens (7, 14, 15) and wider analyses of prokaryote secondary metabolism (41) and its biogeographic distribution (90). However, these studies typically focus on the biosynthetic capacity and associated phylogenetic relationships of globally distributed strains rather than addressing the distribution and dynamics of natural product production for bacteria within a defined geographic region.…”

Section: Discussionmentioning

confidence: 99%

Pan-genome analysis identifies intersecting roles for Pseudomonas specialized metabolites in potato pathogen inhibition

Stefanato

Trippel

Uszkoreit

et al. 2019

Preprint

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23Agricultural soil harbors a diverse microbiome that can form beneficial relationships with plants, 24 including the inhibition of plant pathogens. Pseudomonas are one of the most abundant 25 bacterial genera in the soil and rhizosphere and play important roles in promoting plant growth 26 and preventing disease. However, the genetic determinants of this beneficial activity are only 27 partially understood, especially in relation to specialized metabolite production. Here, we 28 genetically and phenotypically characterize the Pseudomonas fluorescens population in 29 commercial potato field soils and identify strong correlations between specialized metabolite 30 biosynthetic pathways and antagonism of the potato pathogens Streptomyces scabies and 31 Phytophthora infestans. Genetic and chemical analyses identified hydrogen cyanide and cyclic 32 lipopeptides as key specialized metabolites associated with S. scabies inhibition. We show that 33 a single potato field contains a hugely diverse and dynamic population of Pseudomonas 34 bacteria, whose capacity to produce specialized metabolites is shaped both by plant 35 colonization and defined environmental inputs. 36 2 37 CFC agar and incubated overnight at 28 °C before streaking to single colonies on King's B (KB) 595 agar plates (96). Six isolates were selected at random per soil sample and subjected to 596 phenotypic/genomic analysis. 597 598 Amplicon sequencing 599 Genomic DNA was isolated from 3 g of pooled soil samples using the FastDNA™ SPIN Kit for 600 soil (MP Biomedicals, UK) following the manufacturer's instructions. Genomic DNA 601 concentration and purity was determined by NanoDrop spectrophotometry as above. Microbial 602 16S rRNA genes were amplified from soil DNA samples with barcoded universal prokaryotic 603 23 primers (515F/R806) targeting the V4 region, and then subjected to Illumina® MiSeq 604 sequencing (600-cycle, 2x300 bp) at the DNA Sequencing Facility, Department of Biochemistry, 605

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“…156,164,165 Similar to the gene cluster containing PltA, Bmp2 is associated with a thioesterase (TE, Bmp1) and proline adenyltransferase (Bmp4). 156,164 Reconstitution of these enzymes in vitro showed Bmp2 to brominate pyrrole-2-carboxy-S-Bmp1 (32) to mono-, diand tri-bromo products ( Figure 15B).…”

Section: Flavin-dependent Pyrrole Halogenasesmentioning

confidence: 99%

Development of Halogenase Enzymes for Use in Synthesis

Latham

Brandenburger

Shepherd³

et al. 2017

Chem. Rev.

285

244

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Nature has evolved halogenase enzymes to regioselectively halogenate a diverse range of biosynthetic precursors, with the halogens introduced often having a profound effect on the biological activity of the resulting natural products. Synthetic endeavours to create non-natural bioactive small molecules for pharmaceutical and agrochemical applications have also arrived at a similar conclusion -halogens can dramatically improve the properties of organic molecules for selective modulation of biological targets in vivo. Consequently a high proportion of pharmaceuticals and agrochemicals on the market today possess halogens. Halogenated organic compounds are also common intermediates in synthesis and are particularly valuable in metal catalyzed cross-coupling reactions.Despite the potential utility of organohalogens, traditional non-enzymatic halogenation chemistry utilizes deleterious reagents and often lacks regiocontrol. Reliable, facile and cleaner methods for the regioselective halogenation of organic compounds are therefore essential in the development of economical and environmentally-friendly industrial processes. A potential avenue towards such methods is the use of halogenase enzymes, responsible for the biosynthesis of halogenated natural products, as biocatalysts. This review will discuss the advances towards this goal thus far, in addition to untapped potential sources of such biocatalysts and how further development of the enzymes may be focused in order to achieve the goal of industrial scale biohalogenation.

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An Integrated Metabolomic and Genomic Mining Workflow To Uncover the Biosynthetic Potential of Bacteria

Cited by 63 publications

References 84 publications

Impact of Phaeobacter inhibens on marine eukaryote‐associated microbial communities

Impact of Phaeobacter inhibens on marine eukaryote‐associated microbial communities

Pan-genome analysis identifies intersecting roles for Pseudomonas specialized metabolites in potato pathogen inhibition

Development of Halogenase Enzymes for Use in Synthesis

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