Biosynthetic Modularity Rules in the Bisintercalator Family of Antitumor Compounds

Marine Drugs

Javier Fernández¹  Laura Marín¹  Raquel Álvarez-Alonso¹  Saúl Redondo¹  Juan Carvajal¹  Germán Villamizar¹  Claudio J. Villar¹ 

[1] Research Group BITTEN, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, C/Julián Clavería 7, Facultad de Medicina, Oviedo 33006, Spain;

关键词: bisintercalator;    antitumor;    antibiotic;    antiviral;    non-ribosomal peptide;    3-hydroxy-quinaldic acid;    quinoxaline-2-carboxilic acid;    actinomycete;    depsipeptide;    thiodepsipeptide;   

DOI  :  10.3390/md12052668

来源: mdpi

【 摘 要 】

Diverse actinomycetes produce a family of structurally and biosynthetically related non-ribosomal peptide compounds which belong to the chromodepsipeptide family. These compounds act as bisintercalators into the DNA helix. They give rise to antitumor, antiparasitic, antibacterial and antiviral bioactivities. These compounds show a high degree of conserved modularity (chromophores, number and type of amino acids). This modularity and their high sequence similarities at the genetic level imply a common biosynthetic origin for these pathways. Here, we describe insights about rules governing this modular biosynthesis, taking advantage of the fact that nowadays five of these gene clusters have been made public (thiocoraline, triostin, SW-163 and echinomycin/quinomycin). This modularity has potential application for designing and producing novel genetic engineered derivatives, as well as for developing new chemical synthesis strategies. These would facilitate their clinical development.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.