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Mar. Drugs 2014, 12(5), 2668-2699; doi:10.3390/md12052668
Review

Biosynthetic Modularity Rules in the Bisintercalator Family of Antitumor Compounds

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Received: 29 January 2014 / Revised: 9 April 2014 / Accepted: 11 April 2014 / Published: 9 May 2014
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Abstract

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.
Keywords: bisintercalator; antitumor; antibiotic; antiviral; non-ribosomal peptide; 3-hydroxy-quinaldic acid; quinoxaline-2-carboxilic acid; actinomycete; depsipeptide; thiodepsipeptide bisintercalator; antitumor; antibiotic; antiviral; non-ribosomal peptide; 3-hydroxy-quinaldic acid; quinoxaline-2-carboxilic acid; actinomycete; depsipeptide; thiodepsipeptide
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Fernández, J.; Marín, L.; Álvarez-Alonso, R.; Redondo, S.; Carvajal, J.; Villamizar, G.; Villar, C.J.; Lombó, F. Biosynthetic Modularity Rules in the Bisintercalator Family of Antitumor Compounds. Mar. Drugs 2014, 12, 2668-2699.

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