Dual distal insertions drive pimarane-to-miltiradiene rearrangement with enhanced enzymatic activity.

ABSTRACT: Miltiradiene, the major biosynthetic precursor of abietane diterpenoid natural products, has downstream metabolic derivatives with a significant potential for pharmacologically development. The formation of the characteristic abietane skeleton is attained through the rearrangement of the C13 methyl group in the pimarane intermediate, but the key enzyme mechanism responsible for this rearrangement remains elusive. Previous studies have shown that IrKSL3a in Isodon rubescens generates the pimarane diterpene isopimaradiene, and the insertion of two amino acids in the flexible region distal to the enzyme active center can change the enzyme's function to produce the abietane diterpene miltiradiene. In this paper, mutation studies were conducted on another isopimaradiene synthase IrKSL6 i

SUBMITTER: Liu J 

PROVIDER: S-EPMC12710052 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature