The infectious diseases caused by Vibrio species have posed a major challenge in the shrimp aquaculture industry. Owing to the increasing prevalence of multi-drug resistance in Vibrios, newer targets and antibiotics are urgently needed to combat these pathogens. 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) is the first committed enzyme of the methyl erythritolphosphate (MEP) isoprenoid biosynthetic pathway, which is essential for bacteria growth but is absent in hosts. DXR inhibitor fosmidomycin could inhibit the growth of Vibrio vulnificus E1758, and this effect could be reversed by supplementation with isoprenoid precursor isopentenyl diphosphate and DXR product MEP. This finding suggests that DXR is critical for the growth of V. vulnificus and could serve as a potential target for the screening of anti-Vibrio agents. Gene encoding DXR was cloned from V. vulnificus E1758 and overexpressed in Escherichia coli. The recombinant enzyme (rVvDXR) was purified as a soluble protein, and the enzymatic properties and fosmidomycin sensitivity were characterized. Overexpressed rVvDxr can effectively overcome the growth inhibitory effects of fosmidomycin on E. coli, indicating its similar functions to E. coli DXR. A protein-based high throughput screening model was established to identify agents targeting rVvDXR. Methanolic fractions of ethyl acetate extracts from 53 fungal fermentations were subjected for the screening, and hits of interest were confirmed by subsequent enzyme assays. On the basis of the antibacterial activity analysis against three pathogenic Vibrio species and the toxic activity evaluation in brine shrimp Artemia spp., fraction 251-18 obtained from Fusarium oxysporum MCCC 3A00251 was selected for in vivo challenge experiment. A remarkable decrease in mortality was found in the Litopenaeus vannamei post-larvae given with 100 and 200 μg/g fraction-supplemented feed compared with that in the control group fed with un-supplemented feed. These results revealed that DXR can serve a good target for anti-Vibrio agent screening. The application of feed additives with inhibitory effects against DXR may constitute a practical approach to control pathogenic Vibrios for sustainable shrimp cultivation.

由弧菌引起的传染病对虾养殖业构成了重大挑战。由于弧菌对多药耐药性的增加，迫切需要更新的靶标和抗生素来对抗这些病原体。1-脱氧-D-木酮糖-5-磷酸还原异构酶（DXR）是甲基赤藓糖醇磷酸酯（MEP）类异戊二烯生物合成途径的第一个定型酶，它对细菌生长至关重要，但在宿主中却不存在。DXR抑制剂fosmidomycin可以抑制创伤弧菌E1758的生长，并且通过添加类异戊二烯前体异戊烯基二磷酸酯和DXR产物MEP可以逆转这种作用。这一发现表明DXR对于肉豆蔻的生长至关重要。创伤弧菌可作为筛选抗弧菌药物的潜在靶标。编码DXR的基因从V. vulnificus E1758中克隆并在大肠杆菌中过表达。纯化重组酶（rVvDXR）为可溶性蛋白，并表征其酶学性质和磷霉素敏感性。过量表达的rVvDxr可以有效克服fosmidomycin对大肠杆菌的生长抑制作用，表明其功能与大肠杆菌相似。DXR。建立了基于蛋白质的高通量筛选模型，以鉴定靶向rVvDXR的药物。对来自53种真菌发酵的乙酸乙酯提取物的甲醇级分进行筛选，并通过随后的酶分析确认了感兴趣的命中。基于对三种病原弧菌的抗菌活性分析和盐水虾卤虫属物种的毒性活性评估，选择了从尖孢镰刀菌MCCC 3A00251获得的馏分251-18进行体内攻击实验。在南美白对虾中发现死亡率显着降低幼虫后分别添加100和200μg/ g分数添加的饲料，而对照组则未添加。这些结果表明，DXR可以作为抗弧菌药物筛选的良好靶标。使用对DXR具有抑制作用的饲料添加剂可能是控制病原弧菌以实现可持续虾类养殖的实用方法。