Genome Mining of Alkaloidal Terpenoids from a Hybrid Terpene and Nonribosomal Peptide Biosynthetic Pathway

J Am Chem Soc. 2020 Jan 15;142(2):710-714. doi: 10.1021/jacs.9b13046. Epub 2020 Jan 3.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alkaloids / chemistry*
  • Genome*
  • Peptides / chemistry*
  • Ribosomes / chemistry
  • Terpenes / chemistry*

Substances

  • Alkaloids
  • Peptides
  • Terpenes