Unidentified enzymes catalyzing halogenation of sesquiterpene lactones

Identify the biosynthetic halogenating enzymes that introduce halogens into sesquiterpene lactones, including enzymes responsible for the chlorination of guaianolides and heliangolides exemplified by compounds such as chlorohyssopifolin A, cornigeraline A, and lacinolide B.

Background

The paper catalogs multiple halogenated sesquiterpene lactones across diverse taxa, including plants that produce chlorinated guaianolides and heliangolides. Although the chemistry suggests potential involvement of flavin-dependent halogenases acting on hydroxylated intermediates, the specific enzymes remain unknown.

Identifying these halogenases would clarify STL diversification mechanisms and facilitate biosynthetic engineering of halogenated analogs with potential bioactivities.