Deoxysugar pathway interchange for erythromycin analogues heterologously produced through Escherichia coli.
The overall erythromycin biosynthetic pathway can be sub-divided into macrocyclic polyketide formation and polyketide tailoring to produce the final bioactive molecule. In this study, the native deoxysugar tailoring reactions were exchanged for the purpose of demonstrating the production of alternative final erythromycin compounds. Both the d-desosamine and l-mycarose deoxysugar pathways were replaced with the alternative d-mycaminose and d-olivose pathways to produce new erythromycin analogues through the Escherichia coli heterologous system. Both analogues exhibited bioactivity against multiple antibiotic-resistant Bacillus subtilis strains. Besides demonstrating an intrinsic flexibility for the biosynthetic system to accommodate alternative tailoring pathways, the results offer an initial attempt to leverage the E. coli platform for erythromycin analogue production.
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology Shanghai Jiao Tong University, Shanghai 200240, China; Department of Chemical and Biological Engineering, State University of New York at Buffalo, Buffalo, NY 14260, USA.
Ming
M
Jiang
Haoran
H
Zhang
Sung-Hee
SH
Park
Yi
Y
Li
Blaine A
BA
Pfeifer
D000606:Amino Sugars / Q000235:genetics / Q000378:metabolism; D001412:Bacillus subtilis / Q000201:enzymology / Q000235:genetics; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D003837:Deoxy Sugars / Q000235:genetics / Q000378:metabolism; D004917:Erythromycin / Q000031:analogs & derivatives / Q000096:biosynthesis; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D006601:Hexoses; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics
D000606:Amino Sugars; D001426:Bacterial Proteins; D003837:Deoxy Sugars; D006601:Hexoses; D011994:Recombinant Proteins; C045835:mycarose; C013610:mycaminose; C110125:desosamine; D004917:Erythromycin; C407877:olivose; D005944:Glucosamine
Analogue; Antibiotic; Deoxysugar; E. coli; Erythromycin