Revisiting the manzamine biosynthetic hypothesis

Covering: up to 2023 The marine environment represents a rich yet challenging source of novel therapeutics. These challenges are best exemplified by the manzamine class of alkaloids, featuring potent bioactivities, difficult procurement, and a biosynthetic pathway that has eluded characterization for over three decades. This review highlights postulated biogenic pathways toward the manzamines, evaluated in terms of current biosynthetic knowledge and metabolic precedent. A re-evaluation of the biosynthetic hypothesis of the manzamine natural products is discussed. In addition to considering its unified origins with other marine alkaloids, several other plausible biosynthetic hypotheses are critically evaluated.