Sustainable Bioprocessing Approaches for Large-Scale Jadomycin Production

抗生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使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。 Jadomycins显示出作为新型治疗剂的潜力。 当委内瑞拉链霉菌细菌受到压力并提供氨基酸时，会产生不同的jadomycins，为创造药物提供分子支架来源。 雅多霉素工艺有几个阶段：（1）细菌生长，（2）施加环境压力，（3）雅多霉素生产和（4）下游加工。 我们的总体研究目标是开发可持续发酵技术，以实现最佳的大规模生产。 所提出的方法包括评价其他行业的副产品（甘油从生物柴油生产和氨基酸从鱼加工）作为微生物生长和生产介质中的最佳雅多霉素生产的组件。 在雅多霉素生产过程中结合使用甘油和鱼类副产品是一种原创和创新的方式：（1）提高雅多霉素工艺的经济和环境可持续性，（2）改善生物柴油和鱼类加工行业的经济和环境影响。 开发用于雅多霉素生产培养基的鱼源性氨基酸混合物将允许开发一种新的方法，其中可以从单一发酵中生产几种雅多霉素。 通过减少停机时间和提高产品一致性，连续大规模生产杰霉素将具有工业意义。 这项研究将通过开发新药和有效的生产方法使所有加拿大人受益。 它还将使几个高素质的人员（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.