Tetrahydroisoquinoline natural products, biosynthetic pathways, and a novel workflow. a) ET-743 (1) and: saframycin A (2), saframycin Mx1 (3), and safracin (4). b) ET-743 core modular NRPS proteins (EtuA1-3) and previously characterized Sfm, Saf, and Sac NRPS biosynthetic systems. NRPS domains are: AL-acyl ligase, T-thiolation, C-condensation, A-adenylation, RE-reductive. c) The experimental workflow: Ecteinascidia turbinata in its natural environment (Cory Walter, Mote Marine Laboratory) is collected (Erich Bartels, Mote Marine Laboratory), and subjected to meta-omic analysis. ET-743 related secondary metabolites were evaluated by Liquid chromatography FTICR mass spectrometry (LC-FTICR-MS/MS), total metagenomic and 16S DNA by 454 metagenomic sequencing with contig assembly, and total metaproteome by nano-LC-FTICR-MS/MS (nLC) and nLC-Orbitrap-MS/MS.