Elucidation of the glycosylation steps during biosynthesis of antitumor macrolides PM100117 and PM100118 and engineering for novel derivatives. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Salcedo, Raúl; Olano, Carlos; Fernández, Rogelio; Braña, Alfredo; Méndez, Carmen; Calle, Fernando; Salas, José
• Is Part Of: Microbial cell factories. Volume 15:Issue 1(2016)
• Page Start: 1
• Page End: 13
• Publication Date: 2016-12
• Subjects: Antitumor -- Deoxysugar -- Glycosyltranferase -- Structural analogue; Microbial biotechnology -- Periodicals; Recombinant proteins -- Synthesis -- Periodicals; 660.62
• DOI: 10.1186/s12934-016-0591-7
• Languages: English
• ISSNs: 1475-2859

Abstract

Abstract Background Antitumor compounds PM100117 and PM100118 are glycosylated polyketides derived from the marine actinobacteriaStreptomyces caniferus GUA-06-05-006A. The organization and characterization of the PM100117/18 biosynthesis gene cluster has been recently reported. Results Based on the preceding information and new genetic engineering data, we have outlined the pathway by which PM100117/18 are glycosylated. Furthermore, these genetic engineering experiments have allowed the generation of novel PM100117/18 analogues. Deletion of putative glycosyltranferase genes and additional genes presumably involved in late biosynthesis steps of the three 2, 6-dideoxysugars appended to the PM100117/18 polyketide skeleton, resulted in the generation of a series of intermediates and novel derivatives. Conclusions Isolation and identification of the novel compounds constitutes an important contribution to our knowledge on PM100117/18 glycosylation, and set the basis for further characterization of specific enzymatic reactions, additional genetic engineering and combinatorial biosynthesis approaches.