SYNMOD - Synthetic biology to obtain novel antibiotics and optimized production systems

Synmod建议应用综合合成生物学方法来设计和生产新型抗生素分子。首先，进化上预先确定的肽模块被精确定义，然后重新组合成新的抗生素功能。这些模块是从l抗生素组中获得的，翻译后修饰的肽抗生素。接下来，我们将通过利用混杂修饰酶和微调修饰途径的组成来组装上下文不敏感的翻译后机制。这将通过以模块化方式组织路径并提供完全表征的表达元素来实现。然后，该途径将在复杂性较低的新型生产底盘中实施，特别是革兰氏阳性肉葡萄球菌（2.56 Mg基因组），所得菌株将用于生产各种新型抗生素的制备量。因此，通过在工程过程的各个层面上的模块化和上下文不敏感原则，我们试图提供一种具有不同寻常的鲁棒性和可预测性的抗生素设计和生产系统。以这个项目为具体例子，我们将分析合成生物学对生物技术过程安全性的潜在影响及其对我们社会的伦理影响。这些考虑将与公众分享，以建立关于潜在变革性新技术的建设性对话。

Synmod proposes to apply a comprehensive synthetic biology approach to the design and production of novel antibiotic molecules. First, evolutionarily pre-determined peptide modules are precisely defined and then re-combined for novel antibiotic functions. The modules are obtained from the group of lantibiotics, post-translationally modified peptide antibiotics. Next, we will assemble a context-insensitive post-translational machinery by exploiting promiscuous modification enzymes and enabling a fine-tuning of the composition of the modification pathway. This will be obtained by organizing the pathway in a modular fashion and providing thoroughly characterized expression elements. This pathway will then be implemented in a novel production chassis of reduced complexity, specifically the Gram-positive Staphylococcus carnosus (2.56 Mg genome), and the resulting strain will be used to manufacture preparative quantities of a variety of novel lantibiotics. By consequently the principles of modularity and context-insensitivity on the various levels of the engineering process, we attempt to provide a antibiotic design and production system of unusual robustness and predictability. Using this project as a concrete example, we will analyze the potential impact of synthetic biology on the safety of biotechnological processes and its ethical implications for our society. These considerations will be shared with the public to institute a constructive dialogue about a potentially transformative novel technology.