Nielsen Jochem R, Kennerley Joseph, Huang Wei E
Department of Engineering Science, University of Oxford, Oxford, OX1 3PJ, UK.
Oxford SimCell Ltd, Begbroke Science Park, Begbroke, OX5 1PF, UK.
Biotechnol Biofuels Bioprod. 2025 Aug 12;18(1):91. doi: 10.1186/s13068-025-02689-4.
Enzymes capable of catalysing the production of hydrocarbons hold promise for sustainable fuel synthesis. However, the native activities of these enzymes are often insufficient for their exploitation in industrial bioprocesses. Enzyme engineering approaches including directed evolution (DE) can be used to improve the properties of enzymes to meet desirable standards for their industrial application. In this review, we summarise DE methods for engineering hydrocarbon-producing enzymes, including both screening- and selection procedures. The efficacy of DE depends on several factors, including sensitive and accurate detection of enzyme activity, the throughput of screening or selection steps, and the scale of diversity generation. Although DE is a well-established approach, its application in engineering hydrocarbon-producing enzymes has not been widely demonstrated. This can be attributed to the physiochemical properties of the target molecules, such as aliphatic hydrocarbons, which can be insoluble, gaseous, and chemically inert. Detection of these molecules in vivo presents several unique challenges, as does dynamically coupling their abundance to cell fitness. We conclude with a discussion on future directions and potential advancements in this field.
能够催化碳氢化合物生成的酶在可持续燃料合成方面具有广阔前景。然而,这些酶的天然活性往往不足以在工业生物过程中加以利用。包括定向进化(DE)在内的酶工程方法可用于改善酶的特性,以满足其工业应用的理想标准。在本综述中,我们总结了用于工程改造产烃酶的定向进化方法,包括筛选和选择程序。定向进化的效果取决于几个因素,包括酶活性的灵敏准确检测、筛选或选择步骤的通量以及多样性产生的规模。尽管定向进化是一种成熟的方法,但其在工程改造产烃酶方面的应用尚未得到广泛证明。这可归因于目标分子的物理化学性质,如脂肪烃,它们可能不溶、气态且化学惰性。在体内检测这些分子存在几个独特的挑战,将它们的丰度与细胞适应性动态耦合也是如此。我们最后讨论了该领域的未来方向和潜在进展。