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Updated: May 9, 2026

Antimicrobial Peptides Produced by Selective Pressure Incorporation of Non-canonical Amino Acids
Published on: May 4, 2018
An iterative, bimodular nonribosomal peptide synthetase that converts anthranilate and tryptophan into tetracyclic
Xue Gao1, Wei Jiang, Gonzalo Jiménez-Osés
1Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, 420 Westwood Plaza, Los Angeles, CA 90095, USA.
Abstract:
The bimodular 276 kDa nonribosomal peptide synthetase AspA from Aspergillus alliaceus, heterologously expressed in Saccharomyces cerevisiae, converts tryptophan and two molecules of the aromatic β-amino acid anthranilate (Ant) into a pair of tetracyclic peptidyl alkaloids asperlicin C and D in a ratio of 10:1. The first module of AspA activates and processes two molecules of Ant iteratively to generate a tethered Ant-Ant-Trp-S-enzyme intermediate on module two. Release is postulated to involve tandem cyclizations, in which the first step is the macrocyclization of the linear tripeptidyl-S-enzyme, by the terminal condensation (CT) domain to generate the regioisomeric tetracyclic asperlicin scaffolds. Computational analysis of the transannular cyclization of the 11-membered macrocyclic intermediate shows that asperlicin C is the kinetically favored product due to the high stability of a conformation resembling the transition state for cyclization, while asperlicin D is thermodynamically more stable.
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