Sustainable Bioprocessing Approaches for Large-Scale Jadomycin Production

抗菌素耐药性是一个严重的公共卫生问题，推动了对新药的迫切需求。最成功的药物发现途径是利用微生物的天然产物并对其进行化学修饰。有希望的衍生物然后进行动物/临床试验，然而，从发酵中获得足够的材料是一个问题。雅多霉素显示出作为新型治疗剂的潜力。当委内瑞拉链霉菌受到压力并提供氨基酸时，就会产生不同的贾霉素，为制造药物提供分子支架的来源。jadomycin过程有几个阶段：(1)细菌的生长，(2)环境胁迫的应用，(3)jadomycin的生产和(4)下游加工。我们的总体研究目标是开发可持续发酵技术，以优化大规模生产贾霉素。拟议的方法包括评估其他工业的副产品（生物柴油生产的甘油和鱼类加工的氨基酸）作为微生物生长和生产介质的成分，以实现最佳的贾霉素生产。将甘油和鱼类副产品结合使用在贾霉素生产过程中是一种新颖的创新方式，可以：(1)提高贾霉素生产过程的经济和环境可持续性，(2)改善生物柴油和鱼类加工业的经济和环境影响。开发用于贾多霉素生产培养基的鱼源氨基酸混合物将允许开发一种新的程序，其中可以从一次发酵中生产几种贾多霉素。通过减少停机时间和提高产品一致性，连续大规模生产jadomycin将具有工业意义。这项研究将通过开发一种新的药物和有效的生产方法使所有加拿大人受益。它还将使几名高素质人员（HQP）得到培训。

Antimicrobial resistance is a serious public health issue, driving the urgent need for novel drugs. The most successful drug discovery route uses natural products from microbes and chemically modifies them. Promising derivatives then undergo animal/clinical trials, however, obtaining sufficient material from fermentations is an issue. Jadomycins show potential as novel therapeutic agents. When Streptomyces venezuelae bacteria are stressed and supplied with amino acids, different jadomycins are produced, providing a source of molecular scaffolds for creating drugs. The jadomycin process has several stages: (1) growth of bacteria, (2) application of environmental stress, (3) jadomycin production and (4) downstream processing. Our overall research goal is the development of sustainable fermentation technologies for optimal large-scale production of jadomycins. The proposed approach includes the evaluation of by-products from other industries (glycerol from biodiesel production and amino acids from fish processing) as components in microbial growth and production media for optimal jadomycin production. The combined use of glycerol and fish by-products in the jadomycin production process is an original and innovative way to: (1) enhance the economic and environmental sustainability of the jadomycin process and (2) improve the economic and environmental impact of the biodiesel and fish processing industries. The development of a fish-derived amino acid mixture for use in the jadomycin production media will allow a novel procedure to be developed where several jadomycins can be produced from a single fermentation. Continuous large-scale production of jadomycins will have industrial significance via decreased downtime and improved product consistency. This research would benefit all Canadians through the development of a novel drug and efficient production methods. It will also enable several Highly Qualified Personnel (HQP) to be trained.