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物质是一个问题。Jadmycins显示出作为新型治疗药物的潜力。当维尼链霉菌受到压力并提供氨基酸时，会产生不同的绿霉素，为创造药物提供分子支架的来源。杰多霉素的生产过程有几个阶段：(1)细菌的生长，(2)环境胁迫的应用，(3)杰多霉素的生产和(4)下游加工。我们的总体研究目标是开发可持续发酵技术，以实现茉莉菌素的最佳大规模生产。拟议的方法包括对其他行业的副产品(生物柴油生产中的甘油和鱼类加工中的氨基酸)作为微生物生长和生产介质中的成分进行评价，以获得最佳的杰多霉素生产。在杰多霉素生产过程中联合使用甘油和鱼副产品是一种原创性和创新性的方法：(1)提高杰多霉素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。用于杰多霉素生产介质的鱼源性氨基酸混合物的开发将允许开发一种新的工艺，其中可以从一次发酵中生产几种杰多霉素。通过减少停机时间和改善产品一致性，杰多霉素的连续大规模生产将具有工业意义。这项研究将通过开发一种新的药物和高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.