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

Synmod建议将一种全面的合成生物学方法应用于设计和生产新的抗生素分子。首先，精确定义进化上预先确定的多肽模块，然后重新组合以实现新的抗生素功能。所述模块选自经翻译后修饰的多肽抗生素。接下来，我们将通过利用混杂的修饰酶并使修饰途径的组成能够微调来组装一个上下文无关的翻译后机制。这将通过以模块化的方式组织途径并提供完全特征化的表达元件来实现。然后，这一途径将在一种降低复杂性的新型生产底盘中实施，特别是革兰氏阳性肉糖葡萄球菌(2.56毫克基因组)，所产生的菌株将用于生产各种新型抗生素的制备量。因此，通过在工程过程的不同级别上采用模块化和上下文不敏感的原则，我们试图提供具有非凡健壮性和可预测性的抗生素设计和生产系统。以这个项目为例，我们将分析合成生物学对生物技术过程安全的潜在影响，以及它对我们社会的伦理影响。这些考虑将与公众分享，以就一种潜在的变革性新技术展开建设性对话。

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.