Table 1.

Biosynthetic precursors and enzymes confirmed for lupulone or humulone and their derivatives.

Moiety	Precursor	Enzyme(s) involved	Reference
6-carbon ring (structures 1 to 3, Figure 2)	Malonyl-CoA	VPS (valerophenone synthase)	(61, 62)
C-2 acyl side chain to structure 3 (Figure 2)	Isovaleryl-, 2-methylbutyryl, or isobutyryl-CoA	HlCCL2 and HlCCL4 (carboxyl-CoA ligases)	(55)
Alkyl moiety on C-2 acyl side chain of humulone (structure 1a, Figure 2)	Leucine	Enzymes not characterized in refs. 64 or 66; BCAT1 (branched-chain amino transferase) proposed to convert leucine into a precursor of isovaleryl-CoA	(64–66)
Prenyl group on C-4 of structures 1 to 3 (Figure 2)	Deoxyxylulose-5-phosphate in plastidial isoprenoid pathway	Enzymes not characterized in ref. 66; HlPT1 (prenyltransferase) prenylates C-4	(63, 66, 70)
Prenyl group on C-6 of humulone	Deoxyxylulose-5-phosphate in plastidial isoprenoid pathway	Enzymes not characterized in ref. 66; HlPT2 (prenyltransferase) prenylates C-6	(63, 66, 71)
Oxygen on C-6 in humulone and cohumulone (Figure 2, structures 1a and 1b)	Molecular oxygen	Oxygenase; enzyme not characterized	(72)

These have not been confirmed for all the bitter acids listed in Figure 2.