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. 2022 Apr 27;8(5):615–626. doi: 10.1021/acscentsci.1c01389

Figure 1.

Figure 1

Structures of type V GPAs and the schematic biosynthetic pathway of complestatin. (A) Chemical structures of type V GPAs. Type V GPAs are classified by the presence of the conserved central Trp-Hpg-(m)Tyr cross-linked structural motif. Kistamicin has an extra A–O–B ring, and corbomycin has two extra B–C and G–O–H ring structures. Most GPAs are heptapeptides; however, corbomycin and GP6738 represent the only two known nonapeptide GPAs. (B) Complestatin biosynthetic pathway as an example of GPA biosynthesis. The core NRPS scaffold genes (comA-comD), MbtH gene (comE), Na+/H+ antiporter gene (comF), halogenase gene (comH), and P450 monooxygenase genes (comI-comJ) are shown. NRPS domains are labeled as A, adenylation; C, condensation; T, thiolation or peptidyl carrier protein; E, epimerization; MT, methyltransferase; X, Oxy-recruting domain; and TE, thioesterase. The halogenation catalyzed by ComH takes place when the amino acid building block is tethered to the T domain. The characteristic ring cross-linking reactions are performed by specific Oxy proteins as shown. Numbering of the rings on the GPA scaffolds is shown in bold font.