2-Hydroxyacyl-CoA lyase catalyzes acyloin condensation for one-carbon bioconversion.,Nature Chemical Biology

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2-Hydroxyacyl-CoA lyase catalyzes acyloin condensation for one-carbon bioconversion.
Nature Chemical Biology ( IF 12.9 ) Pub Date : 2019-08-05 , DOI: 10.1038/s41589-019-0328-0
Alexander Chou _{1,

2} , James M Clomburg _{1,

2} , Shuai Qian _{1,

3} , Ramon Gonzalez _{1,

2}

Affiliation

Despite the potential of biotechnological processes for one-carbon (C1) bioconversion, efficient biocatalysts required for their implementation are yet to be developed. To address intrinsic limitations of native C1 biocatalysts, here we report that 2-hydroxyacyl CoA lyase (HACL), an enzyme involved in mammalian α-oxidation, catalyzes the ligation of carbonyl-containing molecules of different chain lengths with formyl-coenzyme A (CoA) to produce C1-elongated 2-hydroxyacyl-CoAs. We discovered and characterized a prokaryotic variant of HACL and identified critical residues for this newfound activity, including those supporting the hypothesized thiamine pyrophosphate-dependent acyloin condensation mechanism. The use of formyl-CoA as a C1 donor provides kinetic advantages and enables C1 bioconversion to multi-carbon products, demonstrated here by engineering an Escherichia coli whole-cell biotransformation system for the synthesis of glycolate and 2-hydroxyisobutyrate from formaldehyde and formaldehyde plus acetone, respectively. Our work establishes a new approach for C1 bioconversion and the potential for HACL-based pathways to support synthetic methylotrophy.

中文翻译：

2-Hydroxyacyl-CoA 裂解酶催化 acyloin 缩合进行单碳生物转化。

尽管单碳 (C1) 生物转化的生物技术过程具有潜力，但其实施所需的高效生物催化剂仍有待开发。为了解决天然 C1 生物催化剂的内在局限性，我们在此报告了 2-羟酰基 CoA 裂解酶 (HACL)，一种参与哺乳动物 α-氧化的酶，可催化不同链长的含羰基分子与甲酰基辅酶 A (CoA ) 以生产 C1-延长的 2-羟基酰基-CoA。我们发现并表征了 HACL 的一种原核变体，并确定了这一新发现的活性的关键残基，包括那些支持假设的硫胺素焦磷酸依赖的 acyloin 缩合机制的残基。使用甲酰辅酶 A 作为 C1 供体提供动力学优势并使 C1 生物转化为多碳产物，通过设计大肠杆菌全细胞生物转化系统，分别从甲醛和甲醛加丙酮合成乙醇酸和 2-羟基异丁酸，证明了这一点。我们的工作为 C1 生物转化建立了一种新方法，以及基于 HACL 的途径支持合成甲基营养的潜力。

更新日期：2019-08-05

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