Structural insights and rational engineering strategies for modular polyketide synthases: A review
文献类型：期刊论文
| 作者 | Yu, Wenli4,5; Rao, Jingxin3; Zong, Gongli2; Zhang, Wenchi1; Zheng, Mingyue3; Zhang, Rongzhen4,5 |
| 刊名 | INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
 |
| 出版日期 | 2025-08-01 |
| 卷号 | 319页码:13 |
| 关键词 | Polyketide synthase Structure architecture Rational engineering |
| ISSN号 | 0141-8130 |
| DOI | 10.1016/j.ijbiomac.2025.145299 |
| 通讯作者 | Zhang, Rongzhen(rzzhang@jiangnan.edu.cn) |
| 英文摘要 | Polyketide synthases (PKSs) are among the most complex enzymatic systems in nature, responsible for synthesizing a broad array of polyketides including antibiotics, antifungal agents, and immunosuppressants. CisAcyltransferase (AT) PKSs, distinguished by their multiple modules, diverse catalytic domains, and engineering flexibility, hold significant promise for synthetic biology and natural product discovery. However, even minor alterations to individual domains can propagate structural and functional changes throughout the assembly line, posing a major challenge to the rational design of cis-AT PKSs for diverse polyketides production. This review explores the multidimensionality of cis-AT PKS design, with a focus on the selecting modular building blocks and designing catalytic domains based on the structural and mechanistic insights. Modifications to acyltransferases, ketosynthases, and ketoreductase-dehydratase-enoylreductases can fine-tune substrate specificity and stereochemical complexity, while engineering of the thioesterase domain enables controlled hydrolysis or cyclization for precise polyketide tailoring. Key future directions in cis-AT engineering are also highlighted. Collectively, these insights support the adaptation of cis-AT PKS systems to enhance product yields and expand the repertoire of accessible polyketides. This review provides a systematic overview of cis-AT PKS architecture and engineering strategies, offering a valuable resource for researchers in the field. |
| WOS关键词 | ACYL CARRIER PROTEIN ; ACYLTRANSFERASE DOMAIN ; SUBSTRATE-SPECIFICITY ; CRYSTAL-STRUCTURE ; DEHYDRATASE DOMAINS ; BIOSYNTHESIS ; ERYTHROMYCIN ; MACROCYCLIZATION ; IDENTIFICATION ; SELECTIVITY |
| 资助项目 | National Key Research and Development Program of China[2023YFA0914500] ; National Science Foundation of China[32271487] ; National First-class Discipline Program of Light Industry Technology and Engineering[LITE2018-12] ; Program of Introducing Talents of Discipline to Universities[111-2-06] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry ; Polymer Science |
| 语种 | 英语 |
| WOS记录号 | WOS:001526927900001 |
| 出版者 | ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/318822]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Zhang, Rongzhen |
| 作者单位 | 1.Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA 2.Shandong First Med Univ, Dept Clin Lab, Jinan, Shandong, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China 4.Jiangnan Univ, Key Lab Ind Biotechnol, Minist Educ, Wuxi 214122, Peoples R China 5.Jiangnan Univ, Sch Biotechnol, 1800 Lihu Ave, Wuxi 214122, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yu, Wenli,Rao, Jingxin,Zong, Gongli,et al. Structural insights and rational engineering strategies for modular polyketide synthases: A review[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES,2025,319:13. |
| APA | Yu, Wenli,Rao, Jingxin,Zong, Gongli,Zhang, Wenchi,Zheng, Mingyue,&Zhang, Rongzhen.(2025).Structural insights and rational engineering strategies for modular polyketide synthases: A review.INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES,319,13. |
| MLA | Yu, Wenli,et al."Structural insights and rational engineering strategies for modular polyketide synthases: A review".INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES 319(2025):13. |
入库方式： OAI收割
来源：上海药物研究所
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