A crucial part of overcoming antimicrobial resistance is in the development and overproduction of novel antibiotics. The isolation and genetic analysis of Streptomyces formicae KY5 has identified a wealth of potential with at least 45 biosynthetic gene clusters (BGC) encoded throughout the genome, only a handful of which are produced under standard laboratory conditions and have been attributed to secondary metabolites. Utilisation of various genetic tools including CRISPR/Cas9 mutagenesis and constitutive expression of regulators have previously been shown to effectively manipulate the production of such known compounds, including the formicamycins. Further work on the strain has revealed that continued genetic manipulation can also be used to activate the production of silent BGCs resulting in the production of a broad range of bioactive molecules. Overexpression of autoactive regulators has generated at least five new compounds, which have been analysed through LCMS, and identified another regulator involved in the complex control of formicamycin biosynthesis. Through a combination of RNA-sequencing and ChIP-sequencing we have been able to identify the molecular basis for the production of these compounds and begun to uncover the regulatory mechanism controlling their biosynthetic pathway. We have expanded this technique into the model strains Streptomyces coelicolor and Streptomyces venezualae as well as genetically tractable environmental isolates, with promising results suggesting that this method could be widely utilised to unlock silent BGCs in a myriad of Actinomycetes.