Abstract：
In the green alga Chlamydomonas reinhardtii, hydrogenase HydA1 converts protons and electrons to H2 at the H-cluster, which includes a [4Fe-4S] cluster linked to a [2Fe] cluster. The yield of H2 is limited by the electron transfer to HydA1, mediated by the iron-sulfur unit of a photosynthetic electron transfer ferredoxin (PetF). In this study, I have investigated by molecular dynamics and the hybrid quantum mechanics/molecular mechanics method two canonical iron-sulfur peptides (PM1 and FBM) that hold potential as PetF replacements. Using a docking approach, I predict that the distance between the two iron-sulfur clusters in FBM/HydA1 is shorter than in PM1/HydA1, ensuring a greater electron transfer rate. This finding is in line with the reported higher H2 production rates for FBM/HydA1. I also show that the redox potential of these peptides, and therefore their electron transfer properties, can be changed by single-residue mutations in the secondary coordination sphere of their cluster. In particular, I have designed a PM1 variant that disrupts the hydrogen-bonding network between water and the cluster, shifting the redox potential negatively compared to PM1. These results will guide experiments aimed at replacing PetF with peptides that can unlock the biotechnological potential of the alga.
摘要：
在绿藻莱茵衣藻中，氢化酶HydA1在H团簇处将质子和电子转化为H2，其中包括与[2Fe]簇连接的[4Fe-4S]簇。H2的产量受到电子转移到HydA1的限制，该转移是由光合电子转移铁氧还蛋白（PetF）的铁硫单元介导的。在这项研究中,我已经通过分子动力学和混合量子力学/分子力学方法研究了两种典型的铁硫肽（PM1和FBM），它们具有作为PetF替代品的潜力。使用对接方法，我预测FBM/HydA1中两个铁硫簇之间的距离比PM1/HydA1短，从而确保了更大的电子转移速率。该发现与所报道的FBM/HydA1的较高H2生产率一致。我还显示了这些肽的氧化还原电位，因此它们的电子转移特性，可以通过其簇的二级配位域中的单残基突变来改变。特别是,我设计了一个PM1变体，它破坏了水和团簇之间的氢键网络，与PM1相比，氧化还原电位负向移动。这些结果将指导旨在用可以释放藻类生物技术潜力的肽代替PetF的实验。
