Streptomyces are responsible for the production of two-thirds of clinically relevant antimicrobial agents and understanding control of their biosynthesis will help address the challenge of antimicrobial resistance. Mutations in the bldA locus, which encodes a rare leucyl-tRNA (TTA), results in a complete loss of morphological development and specialised metabolite production.  Thought to be caused by an inability to produce important developmental proteins containing this rare codon, our work, utilizing an RNA aptamer/fluorescent protein construct, showed that transcription and translation of a TTA codon-containing gene in both wild-type and bldA backgrounds can be observed at an early stage in growth when tRNAbldA is unavailable. These data suggest that Wobble base-pairing (WBP) may occur at TTA codons via the TTG leucyl-tRNA (UUG codon) implying that the regulation of this mechanism is not as simple as previously assumed.  Using gene knockouts, over expression mutants, reporter constructs and identified suppressor mutations, we aim to further understand this important mechanism to understand if WBP occurs and its impact on translational efficiency.  In parallel, using mutants we have performed Ribosome-profiling and tRNA-seq to understand the global transcriptional impact and alterations in tRNA modification in the mutant background.  In combination we are testing the the functional limits of WBP and have already shown that it’s possible to complement the bldATTA genetic lesion through over-expression of a WBP match.  Our results suggest that our understanding of this remarkable fine-tuning regulatory mechanism is not complete and has the potential to be exploited in the biotechnology industry.