Natural products are diverse molecules in nature, they are products of living organisms which have huge impact on our wellbeing. A huge number of other diverse potential therapeutics are available from natural products. To date, only a small fraction of these molecules with therapeutic potentials from microbes, plants and marine organisms have been characterized and a lot more work needs to be done to explore the enormous therapeutic potentials from the characterization of new natural product(-like) compounds from the diverse sources. A class of antibiotics are the ribosomally synthesized and post-translationally modified peptides (RIPPs), which include lasso peptide among others. RiPPs are important candidates for bioengineering since they are encoded genetically and generally display wide range of substrate tolerance. We use the precursor peptide of lasso peptide to understand the scope at which the modifying enzymes can modify taking advantage of RIPPs biosynthetic machinery to create new compounds with useful biological activity. Addressing this question, we utilize yeast surface display of precursor peptides and deep sequencing to broadly examine the ability of the modifying enzyme to modify millions of different precursor peptides at once. This approach requires development of screen to identify if the displayed precursor peptide in the yeast cells modify or not. This is achieved by taking advantage of the fact that the leader peptide is removed during lasso peptide modification by looking for the loss of the epitope tag genetically encoded on the peptide.