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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

Previously known clusters identified in the studied marine bacteria, using genome mining. Andrimid gene cluster from V. coralliilyticus S2052 (A); Holomycin gene cluster from P. halotolerans S2753 (B).
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Fig1: Previously known clusters identified in the studied marine bacteria, using genome mining. Andrimid gene cluster from V. coralliilyticus S2052 (A); Holomycin gene cluster from P. halotolerans S2753 (B).

Mentions: The potential for secondary metabolite production in the strains is clearly much larger than so far identified by bioassay-guided fractionation. For instance, the PK/NRP hybrid andrimid has been identified as the bioactive compound in V. coralliilyticus S2052 [28,29,58,59]. The genome mining identified the gene cluster likely encoding for andrimid production genes (Figure 1(A)). Also, we found at least three more NRPS clusters using antiSMASH, NapDos and NP.search (Table 1). Similarly, in P. halotolerans S2753, the dithiolopyrrolone holomycin was identified in extracts [28] and the corresponding gene cluster was found by the bioinformatic tools used (Figure 1(B)); again, four more NRPS/PKS clusters were found using antiSMASH, although only one more was discovered when using NP.search (Table 1). As indicated, we and others have identified several bioactive compounds from pigmented pseudoalteromonads and here we also identified the respective gene clusters for indolmycin [44], violacein [60] and pentabromopseudilin [5,61,62]. However, the pigmented pseudoalteromonads contained a large number of potential bioactive clusters, including a very high number of C-domains as compared to the other studied strains (NapDos – Table 1).Figure 1


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

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

Previously known clusters identified in the studied marine bacteria, using genome mining. Andrimid gene cluster from V. coralliilyticus S2052 (A); Holomycin gene cluster from P. halotolerans S2753 (B).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig1: Previously known clusters identified in the studied marine bacteria, using genome mining. Andrimid gene cluster from V. coralliilyticus S2052 (A); Holomycin gene cluster from P. halotolerans S2753 (B).
Mentions: The potential for secondary metabolite production in the strains is clearly much larger than so far identified by bioassay-guided fractionation. For instance, the PK/NRP hybrid andrimid has been identified as the bioactive compound in V. coralliilyticus S2052 [28,29,58,59]. The genome mining identified the gene cluster likely encoding for andrimid production genes (Figure 1(A)). Also, we found at least three more NRPS clusters using antiSMASH, NapDos and NP.search (Table 1). Similarly, in P. halotolerans S2753, the dithiolopyrrolone holomycin was identified in extracts [28] and the corresponding gene cluster was found by the bioinformatic tools used (Figure 1(B)); again, four more NRPS/PKS clusters were found using antiSMASH, although only one more was discovered when using NP.search (Table 1). As indicated, we and others have identified several bioactive compounds from pigmented pseudoalteromonads and here we also identified the respective gene clusters for indolmycin [44], violacein [60] and pentabromopseudilin [5,61,62]. However, the pigmented pseudoalteromonads contained a large number of potential bioactive clusters, including a very high number of C-domains as compared to the other studied strains (NapDos – Table 1).Figure 1

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