Elucidation of the glycosylation steps during biosynthesis of antitumor macrolides PM100117 and PM100118 and engineering for novel derivatives

作者：Garcia Salcedo Raul; Olano Carlos; Fernandez Rogelio; Brana Alfredo F; Mendez Carmen; de la Calle Fernando; Salas Jose A

来源：Microbial Cell Factories, 2016, 15(1): 187.

DOI：10.1186/s12934-016-0591-7

• Antitumor
• Deoxysugar
• Glycosyltranferase
• Structural analogue

Background: Antitumor compounds PM100117 and PM100118 are glycosylated polyketides derived from the marine actinobacteria Streptomyces 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.

• 出版日期2016-11-9