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Updated: Mar 7, 2026

A Customizable Approach for the Enzymatic Production and Purification of Diterpenoid Natural Products
Published on: October 4, 2019
Molecular and genetic basis for early stage structural diversifications in hapalindole-type alkaloid biogenesis
1Department of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, PA 15260, USA. xinyuliu@pitt.edu.
Abstract:
Heterologous expressions and purifications of all WelU proteins from the welwitindolinone pathways in Hapalosiphon welwitschii UTEX B1830 and IC-52-3 led to the discovery that WelU1 and WelU3 selectively assemble 12-epi-fischerindole U (2) and 12-epi-hapalindole C (1), respectively, from 3-geranyl 3-isocyanovinyl indolenine (4) via an enzymatic cascade featuring the Cope rearrangement, stereoselective aza-Prins cyclization and regioselective carbocation deposition. In combination with the in vitro characterization of WelU1/WelU3-homolog AmbU4 for the biogenesis of 12-epi-hapalindole U, this study provide a unified view on the origin of the early stage structural diversifications in hapalindole-type alkaloid biosynthesis, post common intermediate 4.
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