Search

Meroterpenoids of the ochraceopones family featuring a linear tetracyclic scaffold exhibit exceptional antiviral and anti‐inflammatory activities. The biosynthetic pathway and chemical logic to generate this linear tetracycle, however, remain unknown. In this study, we identified and characterized all biosynthetic enzymes to afford ochraceopones and elucidated the complete biosynthetic pathway. We demonstrated that the linear tetracyclic scaffold of ochraceopones was derived from an angular tetracyclic precursor. A multifunctional cytochrome P450 OchH was validated to catalyze the free‐radical‐initiated carbon‐carbon bond cleavage of the angular tetracycle. Then, a new carbon‐carbon bond was verified to be constructed using a new aldolase OchL, which catalyzes an intramolecular aldol reaction to form the linear tetracycle. This carbon‐carbon bond fragmentation and aldol reaction cascade features an unprecedented strategy for converting a common angular tetracycle to a distinctive linear tetracyclic scaffold in meroterpenoid biosynthesis. [ABSTRACT FROM AUTHOR]

Meroterpenoids of the ochraceopones family featuring a linear tetracyclic scaffold exhibit exceptional antiviral and anti‐inflammatory activities. The biosynthetic pathway and chemical logic to generate this linear tetracycle, however, remain unknown. In this study, we identified and characterized all biosynthetic enzymes to afford ochraceopones and elucidated the complete biosynthetic pathway. We demonstrated that the linear tetracyclic scaffold of ochraceopones was derived from an angular tetracyclic precursor. A multifunctional cytochrome P450 OchH was validated to catalyze the free‐radical‐initiated carbon‐carbon bond cleavage of the angular tetracycle. Then, a new carbon‐carbon bond was verified to be constructed using a new aldolase OchL, which catalyzes an intramolecular aldol reaction to form the linear tetracycle. This carbon‐carbon bond fragmentation and aldol reaction cascade features an unprecedented strategy for converting a common angular tetracycle to a distinctive linear tetracyclic scaffold in meroterpenoid biosynthesis. [ABSTRACT FROM AUTHOR]

The P450 enzyme XiaM was identified as a candidate to form the C-24 carboxyl group in xiamycin A (1). Alteration of medium composition led to the discovery of four new compounds from the ΔxiaMand the ΔxiaK(encoding an aromatic ring hydroxylase) mutants. Biotransformation experiments revealed that XiaM was capable of converting a methyl group to a carboxyl group through diol and aldehyde intermediates. [ABSTRACT FROM AUTHOR]