{"title":"扩大生物合成工具箱:体外 II 型多酮苷合成酶研究的潜力与挑战","authors":"Max A. J. Rivers, Andrew N. Lowell","doi":"10.3390/synbio2010006","DOIUrl":null,"url":null,"abstract":"Type II polyketide synthase (PKS) systems are a rich source of structurally diverse polycyclic aromatic compounds with clinically relevant antibiotic and chemotherapeutic properties. The enzymes responsible for synthesizing the polyketide core, known collectively as the minimal cassette, hold potential for applications in synthetic biology. The minimal cassette provides polyketides of different chain lengths, which interact with other enzymes that are responsible for the varied cyclization patterns. Additionally, the type II PKS enzyme clusters offer a wide repertoire of tailoring enzymes for oxidations, glycosylations, cyclizations, and rearrangements. This review begins with the variety of chemical space accessible with type II PKS systems including the recently discovered highly reducing variants that produce polyalkenes instead of the archetypical polyketide motif. The main discussion analyzes the previous approaches with an emphasis on further research that is needed to characterize the minimal cassette enzymes in vitro. Finally, the potential type II PKS systems hold the potential to offer new tools in biocatalysis and synthetic biology, particularly in the production of novel antibiotics and biofuels.","PeriodicalId":507619,"journal":{"name":"SynBio","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Expanding the Biosynthetic Toolbox: The Potential and Challenges of In Vitro Type II Polyketide Synthase Research\",\"authors\":\"Max A. J. Rivers, Andrew N. Lowell\",\"doi\":\"10.3390/synbio2010006\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Type II polyketide synthase (PKS) systems are a rich source of structurally diverse polycyclic aromatic compounds with clinically relevant antibiotic and chemotherapeutic properties. The enzymes responsible for synthesizing the polyketide core, known collectively as the minimal cassette, hold potential for applications in synthetic biology. The minimal cassette provides polyketides of different chain lengths, which interact with other enzymes that are responsible for the varied cyclization patterns. Additionally, the type II PKS enzyme clusters offer a wide repertoire of tailoring enzymes for oxidations, glycosylations, cyclizations, and rearrangements. This review begins with the variety of chemical space accessible with type II PKS systems including the recently discovered highly reducing variants that produce polyalkenes instead of the archetypical polyketide motif. The main discussion analyzes the previous approaches with an emphasis on further research that is needed to characterize the minimal cassette enzymes in vitro. Finally, the potential type II PKS systems hold the potential to offer new tools in biocatalysis and synthetic biology, particularly in the production of novel antibiotics and biofuels.\",\"PeriodicalId\":507619,\"journal\":{\"name\":\"SynBio\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-03-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"SynBio\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3390/synbio2010006\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"SynBio","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3390/synbio2010006","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
第二类多酮合成酶(PKS)系统是结构多样的多环芳香化合物的丰富来源,具有临床相关的抗生素和化疗特性。负责合成多酮苷核心的酶统称为最小盒,具有在合成生物学中应用的潜力。最小盒提供了不同链长的多酮苷,这些多酮苷与其他酶相互作用,形成了不同的环化模式。此外,II 型 PKS 酶簇还为氧化、糖基化、环化和重排提供了广泛的定制酶。本综述首先介绍了 II 型 PKS 系统可利用的各种化学空间,包括最近发现的可产生多烯而非典型多酮基团的高还原性变体。主要讨论分析了以前的方法,重点是体外鉴定最小盒酶所需的进一步研究。最后,潜在的 II 型 PKS 系统有可能为生物催化和合成生物学,特别是新型抗生素和生物燃料的生产提供新的工具。
Expanding the Biosynthetic Toolbox: The Potential and Challenges of In Vitro Type II Polyketide Synthase Research
Type II polyketide synthase (PKS) systems are a rich source of structurally diverse polycyclic aromatic compounds with clinically relevant antibiotic and chemotherapeutic properties. The enzymes responsible for synthesizing the polyketide core, known collectively as the minimal cassette, hold potential for applications in synthetic biology. The minimal cassette provides polyketides of different chain lengths, which interact with other enzymes that are responsible for the varied cyclization patterns. Additionally, the type II PKS enzyme clusters offer a wide repertoire of tailoring enzymes for oxidations, glycosylations, cyclizations, and rearrangements. This review begins with the variety of chemical space accessible with type II PKS systems including the recently discovered highly reducing variants that produce polyalkenes instead of the archetypical polyketide motif. The main discussion analyzes the previous approaches with an emphasis on further research that is needed to characterize the minimal cassette enzymes in vitro. Finally, the potential type II PKS systems hold the potential to offer new tools in biocatalysis and synthetic biology, particularly in the production of novel antibiotics and biofuels.