Mechanistically, 1 inhibits inosine-5′-monophosphate dehydrogenase; this enzyme catalyzes a knownpathway-regulating step of guanine synthesis, which is essential forlymphocyte proliferation (4). This immunosuppressant is atetraketide-terpenoid (TKTP) compound; this family comprisesvarious chemical structures with a wide spectrum of biologicalactivities (SI Appendix, Fig. S1), and TKTPs are the largest class ofmeroterpenoids produced by filamentous fungi (5). Despite bothits status as one of the oldest natural product antibiotics and thegrowing number of studies reporting the characterization of fungalTKTP biosynthetic pathways (5–8), a full understanding of 1biosynthesis has remained elusive for more than a century.