enzymes encoded by clusters of polyketide synthase and nonribosomal peptide synthetase genes. These chemoenzymatic machineries also exhibit a high level of versatility and capacity for combinatorialization. Genome sequencing have further unveiled more of the combinations and permutations created and selected and many novel polyketides and
nonribosomal peptides remain to be discovered, but there is no direct method for their targeted isolation or for the generalized exploration of their pharmacophores and chemical space. Here, we describe an informatic strategy for automated, targeted detection of predicted or hypothetical natural products based on chemical barcodes and
MS/MS fragmentation. From these approach we have identified several new genetically-envisioned compounds and molecules with desired pharmacophores from complex extracts, leading to the selective isolation of these novel structures. Moreover the work discussed will reveal how new chemoenzymatic routes may be elaborated using metabolomic investigation of natural and unnatural assemblies and engage natural product chemical space towards compounds with improved pharmacological properties.