Figure 6 Structure comparison of SrCYP76AK6-8 andSmCYP76AK1 reveals the divergent evolution.
a Downstream pathway of carnosol and tanshinone biosynthesis,
starting from geranylgeranyl diphosphate. Immediate are shown in
structure and labeled by bold. Enzymes involved in each step are labeled
by italic. The divergence of carnosol and tanshinone biosynthesis start
from 11-hydroxy-ferruginol. CYP76AK6-8 catalyze
11-hydroxy-ferruginol and synthesize carnosol precursors in S.
rosmarinus , which is colored by pink block. CYP76AK1 synthesize
tanshinone precursors in S. miltiorrhiza . Dotted arrows indicate
omitted reaction. b Homology modeling and docking analysis ofSrCYP76AK6-8 and SmCYP76AK1 from S. rosmarinus andS. miltiorrhiza . a Homology modeling ofSrCYP76AK6-1 . Docking poses of SrCYP76AK7-1 b ,SrCYP76AK5-2 c , SrCYP76AK7-2 (d),SrCYP76AK6-2 (e), SrCYP76AK6-3 (f), SmCYP76AK1 (g).
Compound structure is depicted as stick with carbons colored pink and
oxygens red. Heme is depicted as stick with carbons colored yellow and
iron blue. Distance between C-20 and heme iron is indicated by dashed
line with the length indicated in Å. c Residues within 8 Å
around docking sites of SrCYP76AKs , which are different fromSmCYP76AK1 . a Residues pose of SmCYP76AK1 in pink
color and ligand 11-hydroxy-ferruginol in white. Residues pose ofSrCYP76AK5-2 in blue color b , SrCYP76AK6-1 in
yellow c , SrCYP76AK6-2 in green (d). Residues in active
pocket are shown in sticks, with oxygen atom in red, hydrogen in white
and nitrogen atom in blue. Ligand 11-hydroxy-ferruginol is shown in
white sticks. d The expression of SrCYP76AKs andSmCYP76AK1 in roots and leaves. Red, high expression; blue, low
expression. Genes are labeled in italic which are shown based on
functionally annotation in bold. Genes of S. rosmarinus are
marked in green and genes of S. miltiorrhiza are marked in
orange. e Syntenic blocks of CYP76AK regions
within S. rosmarinus, S. miltorrhiza and S. splendens .
Green curves represent the colinearity of CYP76AKs.SrCYP76AK5-8 in S. rosmarinus can be linked toSmCYP76AK1 in S. miltiorrhiza through SsCYP76AK7 inS. splendens , which provide evidence for the evolutionary ofCYP76AK subfamily.