10.1021/jacs.9b09669.s001
Ling Liu
Ling
Liu
Man-Cheng Tang
Man-Cheng
Tang
Yi Tang
Yi
Tang
Fungal Highly Reducing
Polyketide Synthases Biosynthesize
Salicylaldehydes That Are Precursors to Epoxycyclohexenol Natural
Products
American Chemical Society
2019
HRPKS biosynthetic gene clusters
Polyketide Synthases Biosynthesize Salicylaldehydes
HRPKS pathways
β- hydroxyl groups
Trichoderma virens HRPKS gene cluster
enzyme
Epoxycyclohexenol Natural Products Fungal
intramolecular aldol condensation
product trichoxide 1
2019-12-05 19:58:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Fungal_Highly_Reducing_Polyketide_Synthases_Biosynthesize_Salicylaldehydes_That_Are_Precursors_to_Epoxycyclohexenol_Natural_Products/11328083
Fungal highly reducing polyketide synthases (HRPKSs)
are highly
programmed multidomain enzymes that synthesize reduced polyketide
structures. Recent reports indicated salicylaldehydes are synthesized
by HRPKS biosynthetic gene clusters, which are unexpected based on
known enzymology of HRPKSs. Using genome mining of a <i>Trichoderma
virens</i> HRPKS gene cluster that encodes a number of redox
enzymes, we uncover the strategy used by HRPKS pathways in the biosynthesis
of aromatic products such as salicylaldehyde <b>4</b>, which
can be oxidatively modified to the epoxycyclohexanol natural product
trichoxide <b>1</b>. We show selective β-hydroxyl groups
in the linear HRPKS product are individually reoxidized to β-ketones
by short-chain dehydrogenase/reductase enzymes, which enabled intramolecular
aldol condensation and aromatization. Our work expands the chemical
space of natural products accessible through HRPKS pathways.