Department of Biology, Boston College, Chestnut Hill, MA, 02467, USA.
RIKEN Center for Computational Science, Kobe, 6500047, Japan.
Sci Rep. 2023 Jan 17;13(1):860. doi: 10.1038/s41598-023-27519-1.
We investigate laccase-mediated detoxification of aflatoxins, fungal carcinogenic food contaminants. Our experimental comparison between two aflatoxins with similar structures (AFB and AFG) shows significant differences in laccase-mediated detoxification. A multi-scale modeling approach (Docking, Molecular Dynamics, and Density Functional Theory) identifies the highly substrate-specific changes required to improve laccase detoxifying performance. We employ a large-scale density functional theory-based approach, involving more than 7000 atoms, to identify the amino acid residues that determine the affinity of laccase for aflatoxins. From this study we conclude: (1) AFB is more challenging to degrade, to the point of complete degradation stalling; (2) AFG is easier to degrade by laccase due to its lack of side products and favorable binding dynamics; and (3) ample opportunities to optimize laccase for aflatoxin degradation exist, especially via mutations leading to π-π stacking. This study identifies a way to optimize laccase for aflatoxin bioremediation and, more generally, contributes to the research efforts aimed at rational enzyme optimization.
我们研究了漆酶介导的黄曲霉毒素解毒作用，黄曲霉毒素是一种真菌致癌的食物污染物。我们对两种结构相似的黄曲霉毒素（AFB 和 AFG）进行了实验比较，结果表明漆酶介导的解毒作用存在显著差异。采用一种多尺度建模方法（对接、分子动力学和密度泛函理论）确定了提高漆酶解毒性能所需的高度底物特异性变化。我们采用了一种基于大规模密度泛函理论的方法，涉及超过 7000 个原子，以确定决定漆酶与黄曲霉毒素亲和力的氨基酸残基。从这项研究中我们得出结论：（1）AFB 更难降解，甚至完全降解停滞；（2）由于没有副产物和有利的结合动力学，AFG 更容易被漆酶降解；（3）有充分的机会通过导致 π-π 堆积的突变来优化漆酶以降解黄曲霉毒素。这项研究为黄曲霉毒素生物修复中的漆酶优化找到了一种方法，更广泛地说，为旨在合理优化酶的研究工作做出了贡献。
