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Genome mining reveals unlocked bioactive potential of marine Gram-negative bacteria.

Machado H, Sonnenschein EC, Melchiorsen J, Gram L - BMC Genomics (2015)

Bottom Line: The understanding and manipulation of these elements can help in the discovery and production of new compounds never identified under regular laboratory cultivation conditions.High chitinolytic potential was demonstrated and verified for Vibrio and Pseudoalteromonas species that commonly live in close association with eukaryotic organisms in the environment.Chitin regulation by the ChiS histidine-kinase seems to be a general trait of the Vibrionaceae family, however it is absent in the Pseudomonadaceae.

View Article: PubMed Central - PubMed

Affiliation: Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kogle Allè 6, DK-2970, Hørsholm, Denmark. henma@biosustain.dtu.dk.

ABSTRACT

Background: Antibiotic resistance in bacteria spreads quickly, overtaking the pace at which new compounds are discovered and this emphasizes the immediate need to discover new compounds for control of infectious diseases. Terrestrial bacteria have for decades been investigated as a source of bioactive compounds leading to successful applications in pharmaceutical and biotech industries. Marine bacteria have so far not been exploited to the same extent; however, they are believed to harbor a multitude of novel bioactive chemistry. To explore this potential, genomes of 21 marine Alpha- and Gammaproteobacteria collected during the Galathea 3 expedition were sequenced and mined for natural product encoding gene clusters.

Results: Independently of genome size, bacteria of all tested genera carried a large number of clusters encoding different potential bioactivities, especially within the Vibrionaceae and Pseudoalteromonadaceae families. A very high potential was identified in pigmented pseudoalteromonads with up to 20 clusters in a single strain, mostly NRPSs and NRPS-PKS hybrids. Furthermore, regulatory elements in bioactivity-related pathways including chitin metabolism, quorum sensing and iron scavenging systems were investigated both in silico and in vitro. Genes with siderophore function were identified in 50% of the strains, however, all but one harboured the ferric-uptake-regulator gene. Genes encoding the syntethase of acylated homoserine lactones were found in Roseobacter-clade bacteria, but not in the Vibrionaceae strains and only in one Pseudoalteromonas strains. The understanding and manipulation of these elements can help in the discovery and production of new compounds never identified under regular laboratory cultivation conditions. High chitinolytic potential was demonstrated and verified for Vibrio and Pseudoalteromonas species that commonly live in close association with eukaryotic organisms in the environment. Chitin regulation by the ChiS histidine-kinase seems to be a general trait of the Vibrionaceae family, however it is absent in the Pseudomonadaceae. Hence, the degree to which chitin influences secondary metabolism in marine bacteria is not known.

Conclusions: Utilizing the rapidly developing sequencing technologies and software tools in combination with phenotypic in vitro assays, we demonstrated the high bioactive potential of marine bacteria in an efficient, straightforward manner - an approach that will facilitate natural product discovery in the future.

No MeSH data available.


Related in: MedlinePlus

Analysis of the Fur sequences of the marine bacterial strains used. Predicted Fur protein sequence alignment (A); Phylogenetic neighbor joining tree using Jukes-Cantor protein distance measurement method (B).
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Fig2: Analysis of the Fur sequences of the marine bacterial strains used. Predicted Fur protein sequence alignment (A); Phylogenetic neighbor joining tree using Jukes-Cantor protein distance measurement method (B).

Mentions: Even though iron is essential for growth, excess of iron can be toxic to bacteria and thus a tight regulation of uptake is crucial for microbial survival [68]. In Gram-negative bacteria, iron regulation is achieved by a repressor protein named Fur (Ferric-iron uptake regulator) which acts at the transcriptional level [70]. A Fur encoding gene could be identified in all the studied strains and the amino acid sequence predicted, with the sole exception of Paracoccus sp. S4493 (Table 2; Figure 2(A)). The verified exception of Paracoccus sp. S4493 might be due to sequencing limitations, or the fact that this organism has another regulatory protein involved in iron sensing; in fact other uptake regulators for different metals could be identified (e.g. manganese, potassium, zinc, and nickel).Figure 2


Genome mining reveals unlocked bioactive potential of marine Gram-negative bacteria.

Machado H, Sonnenschein EC, Melchiorsen J, Gram L - BMC Genomics (2015)

Analysis of the Fur sequences of the marine bacterial strains used. Predicted Fur protein sequence alignment (A); Phylogenetic neighbor joining tree using Jukes-Cantor protein distance measurement method (B).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4359443&req=5

Fig2: Analysis of the Fur sequences of the marine bacterial strains used. Predicted Fur protein sequence alignment (A); Phylogenetic neighbor joining tree using Jukes-Cantor protein distance measurement method (B).
Mentions: Even though iron is essential for growth, excess of iron can be toxic to bacteria and thus a tight regulation of uptake is crucial for microbial survival [68]. In Gram-negative bacteria, iron regulation is achieved by a repressor protein named Fur (Ferric-iron uptake regulator) which acts at the transcriptional level [70]. A Fur encoding gene could be identified in all the studied strains and the amino acid sequence predicted, with the sole exception of Paracoccus sp. S4493 (Table 2; Figure 2(A)). The verified exception of Paracoccus sp. S4493 might be due to sequencing limitations, or the fact that this organism has another regulatory protein involved in iron sensing; in fact other uptake regulators for different metals could be identified (e.g. manganese, potassium, zinc, and nickel).Figure 2

Bottom Line: The understanding and manipulation of these elements can help in the discovery and production of new compounds never identified under regular laboratory cultivation conditions.High chitinolytic potential was demonstrated and verified for Vibrio and Pseudoalteromonas species that commonly live in close association with eukaryotic organisms in the environment.Chitin regulation by the ChiS histidine-kinase seems to be a general trait of the Vibrionaceae family, however it is absent in the Pseudomonadaceae.

View Article: PubMed Central - PubMed

Affiliation: Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kogle Allè 6, DK-2970, Hørsholm, Denmark. henma@biosustain.dtu.dk.

ABSTRACT

Background: Antibiotic resistance in bacteria spreads quickly, overtaking the pace at which new compounds are discovered and this emphasizes the immediate need to discover new compounds for control of infectious diseases. Terrestrial bacteria have for decades been investigated as a source of bioactive compounds leading to successful applications in pharmaceutical and biotech industries. Marine bacteria have so far not been exploited to the same extent; however, they are believed to harbor a multitude of novel bioactive chemistry. To explore this potential, genomes of 21 marine Alpha- and Gammaproteobacteria collected during the Galathea 3 expedition were sequenced and mined for natural product encoding gene clusters.

Results: Independently of genome size, bacteria of all tested genera carried a large number of clusters encoding different potential bioactivities, especially within the Vibrionaceae and Pseudoalteromonadaceae families. A very high potential was identified in pigmented pseudoalteromonads with up to 20 clusters in a single strain, mostly NRPSs and NRPS-PKS hybrids. Furthermore, regulatory elements in bioactivity-related pathways including chitin metabolism, quorum sensing and iron scavenging systems were investigated both in silico and in vitro. Genes with siderophore function were identified in 50% of the strains, however, all but one harboured the ferric-uptake-regulator gene. Genes encoding the syntethase of acylated homoserine lactones were found in Roseobacter-clade bacteria, but not in the Vibrionaceae strains and only in one Pseudoalteromonas strains. The understanding and manipulation of these elements can help in the discovery and production of new compounds never identified under regular laboratory cultivation conditions. High chitinolytic potential was demonstrated and verified for Vibrio and Pseudoalteromonas species that commonly live in close association with eukaryotic organisms in the environment. Chitin regulation by the ChiS histidine-kinase seems to be a general trait of the Vibrionaceae family, however it is absent in the Pseudomonadaceae. Hence, the degree to which chitin influences secondary metabolism in marine bacteria is not known.

Conclusions: Utilizing the rapidly developing sequencing technologies and software tools in combination with phenotypic in vitro assays, we demonstrated the high bioactive potential of marine bacteria in an efficient, straightforward manner - an approach that will facilitate natural product discovery in the future.

No MeSH data available.


Related in: MedlinePlus