New molecular methods for global activation of cryptic biosynthetic gene clusters

放线菌天然产物是商业用途化合物的重要来源，包括许多临床使用的抗生素、抗真菌和抗癌化合物。产生这些化合物所需的基因是由生物合成基因簇（bgc）编码的。基因组序列数据显示，在编码次级代谢产物的放线菌基因组中存在大量假定沉默的生物合成基因簇，这些基因簇在标准发酵条件下未被检测到。我们已经开发了一个系统，可以促进这些簇的弱生产，并应用于发现新的抗生素和抗真菌化合物。这个项目将使这些方法得到优化，并应用于其他已知或未知功能的bgc。此外，我们将进一步发展这种方法，并将该系统与转座子结合起来，然后将转座子随机插入放线菌的基因组中，从而促进该领域天然产物的生产。该系统可用于提高已知bgc的化合物滴度，并将用于鉴定否则无法检测到的抗生素和抗真菌化合物。该系统将用于多种罕见的放线菌，并诱导出新型抗生素和抗真菌化合物。”

"Actinobacterial Natural Products are an important source of commercially used compounds, including many clinically used antibiotic, antifungal and anticancer compounds. The genes required to produce these compounds are encoded by Biosynthetic Gene Clusters (BGCs). Genomic sequence data have revealed the presence of a large fraction of putatively silent biosynthetic gene clusters in the genomes of actinomycetes that encode for secondary metabolites, which are not detected under standard fermentation conditions.We have developed a system that can boost the weak production from these clusters and has application for the discovery of new antibiotics and antifungal compounds. This project will allow the methods to be optimised and applied to other BGCs of known or unknown function. In addition we will further develop this method and combine the system with a transposon which can then be inserted randomly into the genomes of actinomycetes boosting the production of natural products in this area. The system has application for boosting compound titre from known BGCs and will be used for the identification of otherwise undetectable antibiotic and antifungal compounds. The system will be used on a variety of rare actinomycetes and induced novel antibiotic and antifungal compounds will be characterised."