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

Synmod提出将综合合成生物学方法应用于新型抗生素分子的设计和生产。首先，进化上预先确定的肽模块被精确定义，然后重新组合以获得新的抗生素功能。所述模块获自羊毛硫抗生素（lantibiotics）、后修饰的肽抗生素的组。接下来，我们将组装一个上下文不敏感的翻译后机制，利用混杂的修饰酶，使微调的修饰途径的组成。这将通过以模块化方式组织途径并提供彻底表征的表达元件来获得。然后，该途径将在复杂性降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），并且所得菌株将用于制备制备量的各种新型羊毛硫抗生素。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性的原则，我们试图提供一个抗生素设计和生产系统的不寻常的鲁棒性和可预测性。使用这个项目作为一个具体的例子，我们将分析合成生物学对生物技术过程的安全性及其对我们社会的伦理影响的潜在影响。这些考虑因素将与公众分享，以就潜在的变革性新技术进行建设性对话。

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.