Metabolic dysregulation constitutes a pivotal feature of cancer progression. Enzymes with multiple metal active sites play a major role in this process. Here we report the first metabolic-enzyme-like FeMoO₄ nanocatalyst, dubbed ‘artificial metabzyme’. It showcases dual active centres, namely, Fe²⁺ and tetrahedral Mo⁴⁺, that mirror the characteristic architecture of the archetypal metabolic enzyme xanthine oxidoreductase. Employing spatially dynamic metabolomics in conjunction with the assessments of tumour-associated metabolites, we demonstrate that FeMoO₄ metabzyme catalyses the metabolic conversion of tumour-abundant xanthine into uric acid. Subsequent metabolic adjustments orchestrate crosstalk with immune cells, suggesting a potential therapeutic pathway for cancer. Our study introduces an innovative paradigm in cancer therapy, where tumour cells are metabolically reprogrammed to autonomously modulate and directly interface with immune cells through the intervention of an artificial metabzyme, for tumour-cell-specific metabolic therapy.

代谢失调是癌症进展的关键特征。具有多个金属活性位点的酶在此过程中起着重要作用。在这里，我们报道了第一个类似代谢酶的 FeMoO₄ 纳米催化剂，被称为“人工 metabzyme”。它展示了双活性中心，即 Fe²⁺ 和四面体 Mo⁴⁺，它们反映了原型代谢酶黄嘌呤氧化还原酶的特征结构。将空间动力学代谢组学与肿瘤相关代谢物的评估相结合，我们证明 FeMoO₄ 代谢酶催化肿瘤丰富的黄嘌呤向尿酸的代谢转化。随后的代谢调整协调与免疫细胞的串扰，表明癌症的潜在治疗途径。我们的研究引入了癌症治疗的创新范式，其中肿瘤细胞通过人工代谢酶的干预被代谢重编程为自主调节并直接与免疫细胞连接，以进行肿瘤细胞特异性代谢治疗。