{"title":"Comparative In Silico Structural Analysis of PHA Synthases from industrially Prominent PHA Producers","authors":"Orkun Pinar","doi":"10.1007/s10562-025-04974-1","DOIUrl":null,"url":null,"abstract":"<div><p>Environmental issues from petroleum-based plastics have intensified due to long-term accumulation. Their persistence harms marine and terrestrial life, disrupting food chains, and spreading microplastics. Increased plastic usage driven by industrialization, modern lifestyles, and disposable products contributes to this problem. An effective strategy to mitigate plastic’s negative impact includes waste reduction, recycling, and the development of biodegradable biopolymers. In this sense, polyhydroxyalkanoate (PHA) synthase (PhaC) is a vital enzyme for cost-effective biopolymer/bioplastic production. Thus, this study investigated four different genera (<i>Azotobacter</i>, <i>Bacillus</i>, <i>Cupriavidus</i>, and <i>Halomonas</i>) that are well-known PHA/Polyhydroxybutyrate (PHB) producers, selected due to their proven industrial capability and metabolic versatility in PHA/PHB biosynthesis. Since there has been inadequate information based on the three-dimensional (3D) structures of PHA synthase(s), this is the first report to assess the PHA synthase(s) of these indicated genera by conducting in silico comparative analyses on AlphaFold predicted structures. Furthermore, frustration analysis revealed structural similarities among <i>Azotobacter</i>, <i>Cupriavidus</i>, and <i>Halomonas</i> PHA synthases, while <i>Bacillus</i> exhibited a distinct profile. Identifying highly frustrated residues in potential substrate-binding regions offers insights into their functional dynamics and engineering potential. Molecular docking analysis was also performed to assess interactions between AlphaFold-predicted enzyme structures and their substrates, quantifying the binding energy of enzyme-substrate complexes. The findings of this work will contribute to the engineering of PHA synthase(s) of PHA/PHB producers with the simultaneous understanding of predicted 3D structures using the advanced capabilities of AlphaFold. This understanding will support the creation of more efficient and sustainable bioplastics for the future.</p></div>","PeriodicalId":508,"journal":{"name":"Catalysis Letters","volume":"155 4","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10562-025-04974-1.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Catalysis Letters","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1007/s10562-025-04974-1","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
引用次数: 0
Abstract
Environmental issues from petroleum-based plastics have intensified due to long-term accumulation. Their persistence harms marine and terrestrial life, disrupting food chains, and spreading microplastics. Increased plastic usage driven by industrialization, modern lifestyles, and disposable products contributes to this problem. An effective strategy to mitigate plastic’s negative impact includes waste reduction, recycling, and the development of biodegradable biopolymers. In this sense, polyhydroxyalkanoate (PHA) synthase (PhaC) is a vital enzyme for cost-effective biopolymer/bioplastic production. Thus, this study investigated four different genera (Azotobacter, Bacillus, Cupriavidus, and Halomonas) that are well-known PHA/Polyhydroxybutyrate (PHB) producers, selected due to their proven industrial capability and metabolic versatility in PHA/PHB biosynthesis. Since there has been inadequate information based on the three-dimensional (3D) structures of PHA synthase(s), this is the first report to assess the PHA synthase(s) of these indicated genera by conducting in silico comparative analyses on AlphaFold predicted structures. Furthermore, frustration analysis revealed structural similarities among Azotobacter, Cupriavidus, and Halomonas PHA synthases, while Bacillus exhibited a distinct profile. Identifying highly frustrated residues in potential substrate-binding regions offers insights into their functional dynamics and engineering potential. Molecular docking analysis was also performed to assess interactions between AlphaFold-predicted enzyme structures and their substrates, quantifying the binding energy of enzyme-substrate complexes. The findings of this work will contribute to the engineering of PHA synthase(s) of PHA/PHB producers with the simultaneous understanding of predicted 3D structures using the advanced capabilities of AlphaFold. This understanding will support the creation of more efficient and sustainable bioplastics for the future.
期刊介绍：
Catalysis Letters aim is the rapid publication of outstanding and high-impact original research articles in catalysis. The scope of the journal covers a broad range of topics in all fields of both applied and theoretical catalysis, including heterogeneous, homogeneous and biocatalysis.
The high-quality original research articles published in Catalysis Letters are subject to rigorous peer review. Accepted papers are published online first and subsequently in print issues. All contributions must include a graphical abstract. Manuscripts should be written in English and the responsibility lies with the authors to ensure that they are grammatically and linguistically correct. Authors for whom English is not the working language are encouraged to consider using a professional language-editing service before submitting their manuscripts.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
