Exploiting the Potential of Meroterpenoid Cyclases to Expand the Chemical Space of Fungal Meroterpenoids

Overview

Journal Angew Chem Int Ed Engl

Specialty Chemistry

Date 2020 Sep 15

PMID 32931152

Citations 10

Authors

Takaaki Mitsuhashi

Lena Barra

Zachary Powers

Volga Kojasoy

Andrea Cheng

Feng Yang

Yoshimasa Taniguchi

Takashi Kikuchi

Makoto Fujita

Dean J Tantillo

John A Porco Jr

Ikuro Abe

Affiliations

Soon will be listed here.

Abstract

Fungal meroterpenoids are a diverse group of hybrid natural products with impressive structural complexity and high potential as drug candidates. In this work, we evaluate the promiscuity of the early structure diversity-generating step in fungal meroterpenoid biosynthetic pathways: the multibond-forming polyene cyclizations catalyzed by the yet poorly understood family of fungal meroterpenoid cyclases. In total, 12 unnatural meroterpenoids were accessed chemoenzymatically using synthetic substrates. Their complex structures were determined by 2D NMR studies as well as crystalline-sponge-based X-ray diffraction analyses. The results obtained revealed a high degree of enzyme promiscuity and experimental results which together with quantum chemical calculations provided a deeper insight into the catalytic activity of this new family of non-canonical, terpene cyclases. The knowledge obtained paves the way to design and engineer artificial pathways towards second generation meroterpenoids with valuable bioactivities based on combinatorial biosynthetic strategies.

Citing Articles

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