Extended Data Fig. 2: Limited examples of fungal ATP-grasp enzyme involved in natural product biosynthesis.
From: Enzymatic combinatorial synthesis of E-64 and related cysteine protease inhibitors
a, FsqD from fumisoquin biosynthesis was proposed to activate L-tyrosine to form tyrosyl phosphate. The function of FsqD has not been biochemically characterized. b, AnkG was proposed to be an ATP-grasp enzyme that catalyzes the amide bond formation between L-aspartic acid and NK13650D to form NK13650C based on the in vivo experiments. c, Sequence similarity network analysis of Cp1B homologs from the UniProt database. Note that 5,000 maximum number target sequences from a blastp search with Cp1B as a query (expect threshold value: 5) were retrieved and subjected to SSN construction, with an alignment score threshold of 7. Cp1B and Cp2B in this study and the proposed ATP-grasp enzyme AnkG are highlighted. While Cp1B and Cp2B were located at a separate clade from AnkG, the SSN and the amino acid sequence identity between them ( ~ 30%) suggest these enzymes are distinct but distantly related. While no characterized enzymes were found in this SSN, the SSN showed that putative Cp1B-like ATP-grasp enzymes are conserved in not only many fungi (Ascomycota and Basidiomycota) but also in a few bacteria. Domain abbreviations: A: adenylation; T: peptidyl-carrier protein; R: reductase domain; P: pyridoxal phosphate binding domain.
