In:
Angewandte Chemie International Edition, Wiley, Vol. 62, No. 9 ( 2023-02-20)
Abstract:
(−)‐Antrocin ( 1 ), produced by the medicinal mushroom Antrodia cinnamomea , is a potent antiproliferative compound. The biosynthetic gene cluster of 1 was identified, and the pathway was characterized by heterologous expression. We characterized a haloacid dehalogenase‐like terpene cyclase AncC that biosynthesizes the drimane‐type sesquiterpene (+)‐albicanol ( 2 ) from farnesyl pyrophosphate (FPP). Biochemical characterization of AncC, including kinetic studies and mutagenesis, demonstrated the functions of two domains: a terpene cyclase (TC) and a pyrophosphatase (PPase). The TC domain first cyclizes FPP to albicanyl pyrophosphate, and the PPase domain then removes the pyrophosphate to form 2 . Intriguingly, AncA (94 % sequence identity to AncC), in the same gene cluster, converts FPP into ( R )‐ trans ‐γ‐monocyclofarnesol instead of 2 . Notably, Y283/F375 in the TC domain of AncA serve as a gatekeeper in controlling the formation of a cyclofarnesoid rather than a drimane‐type scaffold.
Type of Medium:
Online Resource
ISSN:
1433-7851
,
1521-3773
DOI:
10.1002/anie.202215566
Language:
English
Publisher:
Wiley
Publication Date:
2023
detail.hit.zdb_id:
2011836-3
detail.hit.zdb_id:
123227-7
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