Biosynthetic pathways containing multiple core enzymes have potential to produce structurally complex natural products. Here we mined a fungal gene cluster that contains two predicted terpene cyclases (TCs) and a nonribosomal peptide synthetase (NRPS). We showed the flv pathway produces flavunoidine 1, an alkaloidal terpenoid. The core of 1 is a tetracyclic, cage-like, and oxygenated sesquiterpene that is connected to dimethylcadaverine via a C-N bond and is acylated with 5,5-dimethyl-l-pipecolate. The roles of all flv enzymes are established on the basis of metabolite analysis from heterologous expression.
Biosynthetic pathways containing multiple core enzymes have potential to produce structurally complex natural products. Here we mined a fungal gene cluster that contains two predicted terpene cyclases (n class="Chemical">TCs) and a nonribosomal peptide synthetase (NRPS). We showed the flv pathway produces flavunoidine 1, an alkaloidal terpenoid. The core of 1 is a tetracyclic, cage-like, and oxygenated sesquiterpene that is connected to dimethylcadaverine via a C-N bond and is acylated with 5,5-dimethyl-l-pipecolate. The roles of all flv enzymes are established on the basis of metabolite analysis from heterologous expression.
Authors: Colin J B Harvey; Mancheng Tang; Ulrich Schlecht; Joe Horecka; Curt R Fischer; Hsiao-Ching Lin; Jian Li; Brian Naughton; James Cherry; Molly Miranda; Yong Fuga Li; Angela M Chu; James R Hennessy; Gergana A Vandova; Diane Inglis; Raeka S Aiyar; Lars M Steinmetz; Ronald W Davis; Marnix H Medema; Elizabeth Sattely; Chaitan Khosla; Robert P St Onge; Yi Tang; Maureen E Hillenmeyer Journal: Sci Adv Date: 2018-04-11 Impact factor: 14.136
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