ACS Chemical Biology最新文献_第2页

PhOxi-seq Detects Enzyme-Dependent m²G in Multiple RNA Types.

IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2024-12-20 Epub Date: 2024-11-29 DOI: 10.1021/acschembio.4c00548

Marie Klimontova, Kimberley Chung Kim Chung, Han Zhang, Tony Kouzarides, Andrew J Bannister, Ryan Hili

引用次数: 0

Biosynthetic Incorporation of Non-native Aryl Acid Building Blocks into Peptide Products Using Engineered Adenylation Domains.

IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2024-12-20 Epub Date: 2024-12-02 DOI: 10.1021/acschembio.4c00663

Fumihiro Ishikawa, Maya Nohara, Akimasa Miyanaga, Satoki Kuramoto, Natsuki Miyano, Shumpei Asamizu, Fumitaka Kudo, Hiroyasu Onaka, Tadashi Eguchi, Genzoh Tanabe

{"title":"Biosynthetic Incorporation of Non-native Aryl Acid Building Blocks into Peptide Products Using Engineered Adenylation Domains.","authors":"Fumihiro Ishikawa, Maya Nohara, Akimasa Miyanaga, Satoki Kuramoto, Natsuki Miyano, Shumpei Asamizu, Fumitaka Kudo, Hiroyasu Onaka, Tadashi Eguchi, Genzoh Tanabe","doi":"10.1021/acschembio.4c00663","DOIUrl":"10.1021/acschembio.4c00663","url":null,"abstract":"Nonribosomal peptides (NRPs), one of the most widespread secondary metabolites in nature, with therapeutically significant activities, are biosynthesized by modular nonribosomal peptide synthetases (NRPSs). Aryl acids contribute to the structural diversity of NRPs as well as nonproteinogenic amino acids and keto acids. We previously confirmed that a single Asn-to-Gly substitution in the 2,3-dihydroxybenzoic acid-activating adenylation (A) domain EntE involved in enterobactin biosynthesis accepts monosubstituted benzoic acid derivatives with nitro, cyano, bromo, and iodo functionalities at the 2 or 3 positions. Here, we showed that the mutant EntE (N235G) accommodates various disubstituted benzoic acid derivatives with halogen, methyl, methoxy, nitro, and cyano functionalities at the 2 and 3 positions and monosubstituted benzoic acid with an alkyne at the 3 position. Structural analysis of the mutant EntE (N235G) with nonhydrolyzable aryl-AMP analogues using 3-chloro-2-methylbenzoic acid and 3-prop-2-ynoxybenzoic acid revealed how bulky 3-chloro-2-methylbenzoic acid and clickable 3-prop-2-ynoxybenzoic acid are recognized by enlarging the substrate-binding pocket of the enzyme. When engineered EntE mutants were coupled with enterobactin and vibriobactin biosynthetic enzymes, 3-hydroxybenzoic acid-, salicylic acid-, and 3-bromo-2-fluorobenzoic acid-containing peptides were produced as early stage intermediates, highlighting the potential of NRP biosynthetic pathway engineering for constructing diverse aryl acid-containing metabolites.","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":"2569-2579"},"PeriodicalIF":3.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Interspecies Crosstalk via LuxI/LuxR-Type Quorum Sensing Pathways Contributes to Decreased Nematode Survival in Coinfections of Pseudomonas aeruginosa and Burkholderia multivorans.

IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2024-12-20 Epub Date: 2024-12-05 DOI: 10.1021/acschembio.4c00641

Betty L Slinger, Samalee Banerjee, Josephine R Chandler, Helen E Blackwell

{"title":"Interspecies Crosstalk via LuxI/LuxR-Type Quorum Sensing Pathways Contributes to Decreased Nematode Survival in Coinfections of Pseudomonas aeruginosa and Burkholderia multivorans.","authors":"Betty L Slinger, Samalee Banerjee, Josephine R Chandler, Helen E Blackwell","doi":"10.1021/acschembio.4c00641","DOIUrl":"10.1021/acschembio.4c00641","url":null,"abstract":"Quorum sensing (QS) is a prominent chemical communication mechanism used by common bacteria to regulate group behaviors at high cell density, including many processes important in pathogenesis. There is growing evidence that certain bacteria can use QS to sense not only themselves but also other species and that this crosstalk could alter collective behaviors. In the current study, we report the results of culture-based and in vivo coinfection experiments that probe interspecies interactions between the opportunistic pathogens Pseudomonas aeruginosa and Burkholderia multivorans involving their LuxI/LuxR-type QS circuits. Using a Caenorhabditis elegans infection model, we show that infections with both species result in poorer host outcomes compared with monoinfections. We use genetic mutants and a transwell infection assay to establish that crosstalk via LuxR-type receptors and signals is important for this coinfection pathogenicity. Using laboratory cocultures with cell-based reporter systems, we show that the RhlR and CepR receptors in P. aeruginosa and B. multivorans, respectively, can each recognize a QS signal produced by the other species. Lastly, we apply chemical biology to complement our genetic approach and demonstrate the potential to regulate interspecies interactions between the wild-type strains of P. aeruginosa and B. multivorans through the application of synthetic compounds that modulate RhlR and CepR activities. Overall, this study reveals that interspecies interaction via QS networks is possible between P. aeruginosa and B. multivorans and that it can contribute to coinfection severity with these two species.","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":"2557-2568"},"PeriodicalIF":3.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Emergence of Oligonucleotide Building Blocks in the Multispecific Proximity-Inducing Drug Toolbox of Destruction.

IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2024-12-20 DOI: 10.1021/acschembio.4c00311

Kevin Xiao Tong Zhou, Katherine E Bujold

{"title":"The Emergence of Oligonucleotide Building Blocks in the Multispecific Proximity-Inducing Drug Toolbox of Destruction.","authors":"Kevin Xiao Tong Zhou, Katherine E Bujold","doi":"10.1021/acschembio.4c00311","DOIUrl":"https://doi.org/10.1021/acschembio.4c00311","url":null,"abstract":"Oligonucleotides are a rapidly emerging class of therapeutics. Their most well-known examples are informational drugs that modify gene expression by binding mRNA. Despite inducing proximity between biological machinery and mRNA when applied to modulating gene expression, oligonucleotides are not typically labeled as \"proximity-inducing\" in literature. Yet, they have recently been explored as building blocks for multispecific proximity-inducing drugs (MPIDs). MPIDs are unique because they can direct endogenous biological machinery to destroy targeted molecules and cells, in contrast to traditional drugs that inhibit only their functions. The unique mechanism of action of MPIDs has enabled the targeting of previously \"undruggable\" molecular entities that cannot be effectively inhibited. However, the development of MPIDs must ensure that these molecules will selectively direct a potent, destruction-based mechanism of action toward intended targets over healthy tissues to avoid causing life-threatening toxicities. Oligonucleotides have emerged as promising building blocks for the design of MPIDs because they are sequence-controlled molecules that can be rationally designed to program multispecific binding interactions. In this Review, we examine the emergence of oligonucleotide-containing MPIDs in the proximity induction space, which has been dominated by antibody and small molecule MPID modalities. Moreover, examples of oligonucleotides developed as MPID candidates in immunotherapy and protein degradation are discussed to demonstrate the utility of oligonucleotides in expanding the scope and selectivity of the MPID toolbox. Finally, we discuss the utility of programming \"AND\" gates into oligonucleotide scaffolds to encode conditional responses that have the potential to be incorporated into MPIDs, which can further enhance their selectivity, thus increasing the scope of this drug category.","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to "Targeting the Early Step of Building Block Organization in Viral Capsid Assembly". 对 "瞄准病毒囊壳组装中积木式组织的早期步骤 "的更正。

IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2024-12-20 Epub Date: 2024-11-28 DOI: 10.1021/acschembio.4c00778

Ayala Lampel, Yaron Bram, Anat Ezer, Ronit Shaltiel-Karyo, Jamil S Saad, Eran Bacharach, Ehud Gazit

引用次数: 0

Intracellular Photocatalytic Proximity Labeling (iPPL) for Dynamic Analysis of Chromatin-Binding Proteins Targeting Histone H3.

IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2024-12-20 Epub Date: 2024-12-09 DOI: 10.1021/acschembio.4c00680

Kazuki Miura, Hikaru Niimi, Tatsuya Niwa, Hideki Taguchi, Hiroyuki Nakamura

引用次数: 0

A Stable Dehydratase Complex Catalyzes the Formation of Dehydrated Amino Acids in a Class V Lanthipeptide. 一种稳定的脱氢酶复合物催化 V 类anthipeptide 中脱水氨基酸的形成。

IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2024-12-20 Epub Date: 2024-11-25 DOI: 10.1021/acschembio.4c00637

George T Randall, Emily S Grant-Mackie, Shayhan Chunkath, Elyse T Williams, Martin J Middleditch, Meifeng Tao, Paul W R Harris, Margaret A Brimble, Ghader Bashiri

{"title":"A Stable Dehydratase Complex Catalyzes the Formation of Dehydrated Amino Acids in a Class V Lanthipeptide.","authors":"George T Randall, Emily S Grant-Mackie, Shayhan Chunkath, Elyse T Williams, Martin J Middleditch, Meifeng Tao, Paul W R Harris, Margaret A Brimble, Ghader Bashiri","doi":"10.1021/acschembio.4c00637","DOIUrl":"10.1021/acschembio.4c00637","url":null,"abstract":"Lanthipeptides are ribosomally synthesized and post-translationally modified peptides that bear the characteristic lanthionine (Lan) or methyllanthionine (MeLan) thioether linkages. (Me)Lan moieties bestow lanthipeptides with robust stability and diverse antimicrobial, anticancer, and antiallodynic activities. Installation of (Me)Lan requires dehydration of serine and threonine residues to 2,3-dehydroalanine (Dha) and (Z)-2,3-dehydrobutyrine (Dhb), respectively. LxmK and LxmY enzymes comprise the biosynthetic machinery of a newly discovered class V lanthipeptide, lexapeptide, and are proposed to catalyze the dehydration of serine and threonine residues in the precursor peptide. We demonstrate that LxmK and LxmY form a stable dehydratase complex to dehydrate precursor peptides. In addition, we present crystal structures of the LxmKY heterodimer, revealing structural and mechanistic features that enable iterative phosphorylation and elimination by the LxmKY complex. These findings provide molecular insights into class V lanthionine synthetases and lay the foundation for their applications as enzymatic tools in the biosynthesis of exquisitely modified peptides.","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":"2548-2556"},"PeriodicalIF":3.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142714756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to "Structure and Biosynthesis of Hectoramide B, a Linear Depsipeptide from Marine Cyanobacterium Moorena producens JHB Discovered via Coculture with Candida albicans". 更正 "通过与白色念珠菌共培养发现的海洋蓝藻 Moorena producens JHB 的线性去肽 Hectoramide B 的结构和生物合成"。

IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2024-12-20 Epub Date: 2024-11-26 DOI: 10.1021/acschembio.4c00739

Thuan-Ethan Ngo, Andrew Ecker, Byeol Ryu, Aurora Guild, Ariana Remmel, Paul D Boudreau, Kelsey L Alexander, C Benjamin Naman, Evgenia Glukhov, Nicole E Avalon, Vikram V Shende, Lamar Thomas, Samira Dahesh, Victor Nizet, Lena Gerwick, William H Gerwick

引用次数: 0

Characterization of a Dual Function Peptide Cyclase in Graspetide Biosynthesis.

IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2024-12-20 Epub Date: 2024-12-04 DOI: 10.1021/acschembio.4c00626

Garret M Rubin, Krishna P Patel, Yujia Jiang, Alivia C Ishee, Gustavo Seabra, Steven D Bruner, Yousong Ding

{"title":"Characterization of a Dual Function Peptide Cyclase in Graspetide Biosynthesis.","authors":"Garret M Rubin, Krishna P Patel, Yujia Jiang, Alivia C Ishee, Gustavo Seabra, Steven D Bruner, Yousong Ding","doi":"10.1021/acschembio.4c00626","DOIUrl":"10.1021/acschembio.4c00626","url":null,"abstract":"Graspetides are a diverse family of ribosomally synthesized and post-translationally modified peptides with unique macrocyclic structures formed by ATP-grasp enzymes. Group 11 graspetides, including prunipeptin, feature both macrolactone and macrolactam cross-links. Despite the known involvement of a single ATP-grasp cyclase in the dual macrocyclizations of groups 5, 7, and 11 graspetides, detailed mechanistic insights into these enzymes remain limited. Here, we reconstructed prunipeptin biosynthesis from Streptomyces coelicolor using recombinant PruA and PruB macrocyclase. PruB exhibited kinetic behavior similar to other characterized graspetide cyclases, with a notably higher kcat, likely due to utilization of an ATP-regeneration system. The X-ray crystal structure of PruB revealed distinct features as compared to groups 1 and 2 enzymes. Site-directed mutagenesis identified critical roles of key residues for the PruB reaction, including the DxR motif conserved in other graspetide cyclases. Additionally, computational modeling of the PruA/PruB cocomplex uncovered substrate interactions and suggested that PruB first catalyzes a macrolactone bond formation on PruA. This study enhances our understanding of ATP-grasp enzyme mechanisms in graspetide biosynthesis and provides insights for engineering these enzymes for future applications.","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":"2525-2534"},"PeriodicalIF":3.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bioorthogonal Cyclopropenones for Investigating RNA Structure.

IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2024-12-20 Epub Date: 2024-12-06 DOI: 10.1021/acschembio.4c00633

Sharon Chen, Christopher D Sibley, Brandon Latifi, Sumirtha Balaratnam, Robert S Dorn, Andrej Lupták, John S Schneekloth, Jennifer A Prescher

{"title":"Bioorthogonal Cyclopropenones for Investigating RNA Structure.","authors":"Sharon Chen, Christopher D Sibley, Brandon Latifi, Sumirtha Balaratnam, Robert S Dorn, Andrej Lupták, John S Schneekloth, Jennifer A Prescher","doi":"10.1021/acschembio.4c00633","DOIUrl":"10.1021/acschembio.4c00633","url":null,"abstract":"RNA sequences encode structures that impact protein production and other cellular processes. Misfolded RNAs can also potentiate disease, but a complete picture is lacking. To establish more comprehensive and accurate RNA structure-function relationships, new methods are needed to interrogate RNA in native environments. Existing tools rely primarily on electrophiles that are constitutively \"on\" or triggered by UV light, often resulting in high background. Here we describe an alternative, chemically triggered approach to cross-link RNAs using bioorthogonal cyclopropenones (CpOs). These reagents selectively react with phosphines to provide ketenes─electrophiles that can trap neighboring nucleophiles to forge covalent cross-links. As a proof-of-concept, we conjugated a CpO motif to thiazole orange (TO-1). TO-1-CpO bound selectively to a model RNA aptamer (Mango) with nanomolar affinity, as confirmed by fluorescence turn-on. After phosphine administration, covalent cross-links were formed between the CpO and RNA. Cross-linking was both time and dose dependent. We further applied the chemically triggered tools to model RNAs under biologically relevant conditions. Collectively, this work expands the toolkit of probes for studying RNA and its native conformations.","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":"2406-2411"},"PeriodicalIF":3.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0