Structural Insights into Novel Thiolases for Enhancing the Production of Tailored Biochemicals

IF 13.1 1区 化学 Q1 CHEMISTRY, PHYSICAL ACS Catalysis Pub Date : 2024-12-30 DOI:10.1021/acscatal.4c05635
Jiyeon Hong, Hyeoncheol Francis Son, So-Young Park, Jiyoung Park, Hogyun Seo, Kwang-Hyeon Liu, Kyung-Jin Kim
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Abstract

Thiolase is essential in the first step of synthesizing many value-added biochemicals. However, only a few feasible THLs have been reported, and a limited understanding of these enzymes has restricted their broader application in valuable production processes. In this study, biochemical and structural analysis identified the specific properties of THLs belonging to three groups for synthesizing medium- to long-chain fatty acids, polyketide, and dicarboxylic acid, represented by adipic acid. We further demonstrated that hydrolysis activity, considered a rate-limiting step in the biosynthetic process, can be alleviated through flux balance and site-directed mutagenesis. Notably, we discovered two THLs with strong biosynthetic abilities and low hydrolysis: PaTHL4, effective for medium- to long-chain fatty acids and polyketides, and PaTHL7, tailored for adipic acid production. This study provides valuable insights into tailored THLs for specific biochemical production.

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新型硫醇酶的结构洞察,以提高定制生化产品的生产
硫醇酶在合成许多高附加值生物化学物质的第一步至关重要。然而,只有少数可行的thl被报道,并且对这些酶的有限了解限制了它们在有价值的生产过程中的广泛应用。在本研究中,通过生化和结构分析,确定了以己二酸为代表的用于合成中长链脂肪酸、聚酮和二羧酸的三组thl的特异性。我们进一步证明,水解活性,被认为是生物合成过程中的限速步骤,可以通过通量平衡和定点诱变来缓解。值得注意的是,我们发现了两个具有强生物合成能力和低水解的thl: PaTHL4,对中长链脂肪酸和聚酮有效,以及PaTHL7,专门用于己二酸的生产。这项研究为特定生化生产量身定制thl提供了有价值的见解。
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来源期刊
ACS Catalysis
ACS Catalysis CHEMISTRY, PHYSICAL-
CiteScore
20.80
自引率
6.20%
发文量
1253
审稿时长
1.5 months
期刊介绍: ACS Catalysis is an esteemed journal that publishes original research in the fields of heterogeneous catalysis, molecular catalysis, and biocatalysis. It offers broad coverage across diverse areas such as life sciences, organometallics and synthesis, photochemistry and electrochemistry, drug discovery and synthesis, materials science, environmental protection, polymer discovery and synthesis, and energy and fuels. The scope of the journal is to showcase innovative work in various aspects of catalysis. This includes new reactions and novel synthetic approaches utilizing known catalysts, the discovery or modification of new catalysts, elucidation of catalytic mechanisms through cutting-edge investigations, practical enhancements of existing processes, as well as conceptual advances in the field. Contributions to ACS Catalysis can encompass both experimental and theoretical research focused on catalytic molecules, macromolecules, and materials that exhibit catalytic turnover.
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