Predictions to Increase Lasso Peptide Production in the Heterologous Host Streptomyces coelicolor M1152 DOI Open Access
Valeria Razmilic, Juan A. Asenjo, Irene Martínez

et al.

Biotechnology and Bioengineering, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 29, 2024

ABSTRACT Production of specialized metabolites are restricted to the metabolic capabilities organisms. Genome‐scale models (GEM)s useful study whole metabolism and find engineering targets increase yield a target compound. In this work we use modified model Streptomyces coelicolor M145 simulate production lagmysin A (LP4) novel B (LP2) lasso peptide, in heterologous host M1152. Overexpression were identified using flux scanning based on enforced objective (FSEOF) algorithm variability analysis (FVA), considering growth minimum complex medium. Thirteen reactions found as candidate for both peptides settings. We propose overexpression enzymes glycolysis pathway (GAPD, PGK, PGM ENO) leucine biosynthesis (IPPS, IPPMIb, IPPMIa, IPMD OMCDC) enhance either or B.

Language: Английский

A broad-spectrum lasso peptide antibiotic targeting the bacterial ribosome DOI
Manoj Jangra, Dmitrii Y. Travin, Elena V. Aleksandrova

et al.

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Language: Английский

Citations

3
Phenotypic and Complete Reference Whole Genome Sequence Analyses of Two Paenibacillus spp. Isolates from a Gray Wolf (Canis lupus) Gastrointestinal Tract DOI Creative Commons
J. Bryant, Jennifer A. McCabe, C. Cristoph Klews

et al.

Veterinary Sciences, Journal Year: 2025, Volume and Issue: 12(1), P. 51 - 51

Published: Jan. 13, 2025

Inflammatory bowel disease (IBD) is increasing among mammals around the world, and domestic dogs are no exception. There approved cure for canine IBD with limited treatment options. Novel probiotic bacteria discovery from free-ranging animals of in pets can likely yield promising candidates. Consequently, overall aim was to isolate that could potentially be utilized as novel probiotics. Two identified unique Paenibacillus spp. strains by small ribosomal RNA (16S) gene sequencing were isolated gastrointestinal tract a North American Gray Wolf (Canis lupus). The typed Gram-variable, both catalase/oxidase positive well sensitive commonly used antibiotics. digested complex carbohydrates lipids standard assays. also inhibited growth Staphylococcus aureus Micrococcus luteus. whole genome sequence (WGS) length bacterial ClWae17B 6,939,193 bp, while ClWae19 7,032,512 similar size other genomes encoded enzymes involved metabolism starches lipids, such lyases pectinases, along encoding antimicrobials lanthipeptides, lasso peptides, cyclic-lactone-autoinducers. No pernicious virulence genes WGS either isolate. Phylogenetically, most closely related based on 16S sequences P. taichungensis amylolyticus ClWae19. analyses phenotypic assays supported hypothesis isolates described constitute two candidate potential use dogs.

Language: Английский

Citations

0
Genome mining and heterologous expression reveal streptacidin, a new lasso peptide from Streptacidiphilus jiangxiensis DOI
Ji‐Wu Huang, Botao Cheng,

Chunyang Cao

et al.

Organic & Biomolecular Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

We heterologously produced a type II lasso peptide gene cluster that was mined from Streptacidiphilus jiangxiensis in E. coli . Streptacidin is the first documented to maintain its 3D structure with methionine as steric lock.

Language: Английский

Citations

0
Overcoming Immune Checkpoint Inhibitor Resistance via Potent and Selective Dual αvβ6/8 Inhibitors Based on Engineered Lasso Peptides DOI Creative Commons
Anna Lechner, Peter A. Jordan, Gabriella Costa Machado da Cruz

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Abstract Integrins αvβ6 and αvβ8 in the tumor microenvironment (TME) have been shown to activate immunosuppressive TGF-β, which serves as an important mechanism for immune checkpoint inhibitor resistance a range of tumors. In this study, we demonstrate utility lasso peptides versatile scaffolds designing new therapeutics. A series highly potent selective dual αvβ6/8 inhibitors were engineered through combination epitope scanning, computational design, directed evolution. Several analogs, such lassotides 36 47 , fully characterized physicochemical, vitro pharmacological, vivo data are reported. Lassotide half-life extended derivative was strongly sensitize anti-mPD-1-resistant tumors mice when dosed with inhibitor. The /anti-mPD-1 halt growth regress mouse models triple negative breast ovarian cancers. Dual inhibition integrins expressed TME thus represents promising tumor-specific strategy overcome TGF-β-driven enhance anti-tumor efficacy inhibitors.

Language: Английский

Citations

0
Deep Learning-Assisted Discovery of Protein Entangling Motifs DOI
Puqing Deng,

Lianjie Xu,

Ying Wei

et al.

Biomacromolecules, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

Natural topological proteins exhibit unique properties including enhanced stability, controlled quaternary structures, and dynamic switching properties, highlighting topology as a dimension in protein engineering. Although artificial design synthesis of have achieved certain success, their diversity complexity remain rather limited due to the scarcity available entangling motifs essential for construction nontrivial topologies. In this work, we developed deep-learning model predict entanglement features homodimer based solely on its amino acid sequence via Gauss linking number matrices. The search speed that was dozens times faster than AlphaFold-Multimer, while maintaining comparable mean squared error. It used screen from genome hyperthermophilic archaeon. We demonstrated effectiveness our by successful wet-lab catenanes using two candidate motifs. These findings show great potential advancing novel proteins.

Language: Английский

Citations

0
Biosynthesis of Collinodin Unveils Iterative Oxidative and Prenylation Modifications DOI
Jing Shi, Yi Zhang, Wenjie Ren

et al.

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 6628 - 6639

Published: April 8, 2025

Language: Английский

Citations

0
Lasso peptides: A focus on therapeutic index DOI

Melika Kolahdoozan,

Ali Jahanian‐Najafabadi

World Journal of Microbiology and Biotechnology, Journal Year: 2025, Volume and Issue: 41(5)

Published: April 28, 2025

Language: Английский

Citations

0
LassoESM: A tailored language model for enhanced lasso peptide property prediction DOI Creative Commons
Xuenan Mi, Susanna E. Barrett, Douglas A. Mitchell

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 29, 2024

Abstract Ribosomally synthesized and post-translationally modified peptides (RiPPs) comprise a structurally functionally diverse group of natural products. Lasso represent one about 50 known molecular classes RiPPs, which display characteristic [1] rotaxane conformation formed by lasso cyclase. This unique, threaded endows with biological activities remarkable thermal proteolytic stability. The prediction peptide properties, such as substrate compatibility particular cyclase or desired activity, remains challenging due to limited experimental data the intricate nature fitness landscapes. Protein language models (PLMs) have demonstrated impressive performance in predicting protein structure function. However, general-purpose PLMs perform poorly peptide-related predictive tasks. Therefore, there is need provide effective representations for enable enhanced property prediction. In this study, we developed peptide-specific model (LassoESM) leveraging advances pre-trained aid related properties experimentally validate predictions. We demonstrate that LassoESM embeddings can accurately predict interest when training was scarce. Using deep learning framework incorporating cross-attention between embeddings, identify non-cognate pairs cyclases predicted compatibility. further show improve RNA polymerase inhibitory represents activity several peptides. anticipate future iterations thereof will be instrumental rational design properties.

Language: Английский

Citations

1
Predictions to Increase Lasso Peptide Production in the Heterologous Host Streptomyces coelicolor M1152 DOI Open Access
Valeria Razmilic, Juan A. Asenjo, Irene Martínez

et al.

Biotechnology and Bioengineering, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 29, 2024

ABSTRACT Production of specialized metabolites are restricted to the metabolic capabilities organisms. Genome‐scale models (GEM)s useful study whole metabolism and find engineering targets increase yield a target compound. In this work we use modified model Streptomyces coelicolor M145 simulate production lagmysin A (LP4) novel B (LP2) lasso peptide, in heterologous host M1152. Overexpression were identified using flux scanning based on enforced objective (FSEOF) algorithm variability analysis (FVA), considering growth minimum complex medium. Thirteen reactions found as candidate for both peptides settings. We propose overexpression enzymes glycolysis pathway (GAPD, PGK, PGM ENO) leucine biosynthesis (IPPS, IPPMIb, IPPMIa, IPMD OMCDC) enhance either or B.

Language: Английский

Citations

0