Quinolizidomycins A (1) and B (2), two unprecedented quinolizidine alkaloids featuring a tricyclic 6/6/5 ring system, were isolated from Streptomyces sp. KIB-1714. Their structures were assigned by detailed spectroscopic data analyses and X-ray diffraction. Stable isotope labeling experiments suggested that compounds 1 and 2 are derived from lysine, ribose 5-phosphate, and acetate units, which indicates an unprecedented manner of assembly of the quinolizidine (1-azabicyclo[4.4.0]decane) scaffold in quinolizidomycin biosynthesis. Quinolizidomycin A (1) was active in an acetylcholinesterase inhibitory assay.