Biosynthetic systems producing fungal indole alkaloids

US9650656B2 · kind B2 · utility

Assignees

• THE REGENTS OF THE UNIVERSITY OF MICHIGAN · US
• COLORADO STATE UNIVERSITY RESEARCH FOUNDATION · US

Inventors

• Shengying Li · 柳山镇, CN
• Krithika Anand Srinivasan · Ann Arbor, US
• Robert M. Williams · Chesterfield, US
• David H. Sherman · Ann Arbor, US

Key dates

• Filing date: Apr 3, 2013
• Grant date: May 16, 2017
• Expiry date: May 17, 2033

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12Y603/02
• WIPO field: Biotechnology
• WIPO sector: Chemistry

Abstract

The biosynthesis of fungal bicyclo[2.2.2]diazaoctane indole alkaloids with a wide spectrum of biological activities have attracted increasing interest. Their intriguing mode of assembly has long been proposed to feature a non-ribosomal peptide synthetase, a presumed intramolecular Diels-Alderase, a variant number of prenyltransferases, and a series of oxidases responsible for the diverse tailoring modifications of their cyclodipeptide-based structural core. Until recently, the details of these biosynthetic pathways have remained largely unknown due to lack of information on the fungal derived biosynthetic gene clusters. Herein, we report a comparative analysis of four natural product metabolic systems of a select group of bicyclo[2.2.2]diazaoctane indole alkaloids including (+)/(−)-notoamide, paraherquamide and malbrancheamide, in which we propose an enzyme for each step in the biosynthetic pathway based on deep annotation and on-going biochemical studies.