| Title |
Phylogeny-guided genome mining of roseocin family lantibiotics to generate improved variants of roseocin
|
|---|---|
| Published in |
AMB Express, March 2023
|
| DOI | 10.1186/s13568-023-01536-9 |
| Pubmed ID | |
| Authors |
Sandeep Chaudhary, Shweta Kishen, Mangal Singh, Sunanda Jassal, Reeva Pathania, Kalpana Bisht, Dipti Sareen |
| Abstract |
Roseocin, the two-peptide lantibiotic from Streptomyces roseosporus, carries extensive intramolecular (methyl)lanthionine bridging in the peptides and exhibits synergistic antibacterial activity against clinically relevant Gram-positive pathogens. Both peptides have a conserved leader but a diverse core region. The biosynthesis of roseocin involves post-translational modification of the two precursor peptides by a single promiscuous lanthipeptide synthetase, RosM, to install an indispensable disulfide bond in the Rosα core along with four and six thioether rings in Rosα and Rosβ cores, respectively. RosM homologs in the phylum actinobacteria were identified here to reveal twelve other members of the roseocin family which diverged into three types of biosynthetic gene clusters (BGCs). Further, the evolutionary rate among the BGC variants and analysis of variability within the core peptide versus leader peptide revealed a phylum-dependent lanthipeptide evolution. Analysis of horizontal gene transfer revealed its role in the generation of core peptide diversity. The naturally occurring diverse congeners of roseocin peptides identified from the mined novel BGCs were carefully aligned to identify the conserved sites and the substitutions in the core peptide region. These selected sites in the Rosα peptide were mutated for permitted substitutions, expressed heterologously in E. coli, and post-translationally modified by RosM in vivo. Despite a limited number of generated variants, two variants, RosαL8F and RosαL8W exhibited significantly improved inhibitory activity in a species-dependent manner compared to the wild-type roseocin. Our study proves that a natural repository of evolved variants of roseocin is present in nature and the key variations can be used to generate improved variants. |
X Demographics
The data shown below were collected from the profiles of 7 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 2 | 29% |
| Hungary | 1 | 14% |
| Unknown | 4 | 57% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 3 | 43% |
| Members of the public | 3 | 43% |
| Science communicators (journalists, bloggers, editors) | 1 | 14% |
Mendeley readers
The data shown below were compiled from readership statistics for 14 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 14 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Unspecified | 1 | 7% |
| Student > Ph. D. Student | 1 | 7% |
| Researcher | 1 | 7% |
| Other | 1 | 7% |
| Student > Postgraduate | 1 | 7% |
| Other | 0 | 0% |
| Unknown | 9 | 64% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 3 | 21% |
| Unspecified | 1 | 7% |
| Agricultural and Biological Sciences | 1 | 7% |
| Unknown | 9 | 64% |
Attention Score in Context
This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 March 2024.
All research outputs
#7,233,458
of 25,621,213 outputs
Outputs from AMB Express
#130
of 1,330 outputs
Outputs of similar age
#126,883
of 423,510 outputs
Outputs of similar age from AMB Express
#2
of 14 outputs
Altmetric has tracked 25,621,213 research outputs across all sources so far. This one has received more attention than most of these and is in the 71st percentile.
So far Altmetric has tracked 1,330 research outputs from this source. They receive a mean Attention Score of 3.2. This one has done particularly well, scoring higher than 90% of its peers.
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We're also able to compare this research output to 14 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 92% of its contemporaries.