Figure 8.

Proposed momilactone A biosynthetic pathway. This pathway is initiated by the cyclization reactions catalyzed by OsCPS4 and OsKSL4 to form 1, with subsequent formation of the 19-aldehyde derivative 6 catalyzed by CYP99A2 or CYP99A3, then further 6β-hydroxylation catalyzed by CYP7M8 forming 8, followed by spontaneous formation of the 19,6β-hemiacetal 9, then oxidization to the 19,6β-lactone 10 catalyzed by OsMS1 or OsMS2, with the final 3β-hydroxylation catalyzed by CYP701A8, which may also catalyze further oxidation to the 3-keto containing momilactone A (12), a step that can also be catalyzed by OsMS2.