Heterologous expression of galbonolide biosynthetic genes in Streptomyces coelicolor

Antonie van Leeuwenhoek
Chao LiuYuemao Shen

Abstract

The galbonolide antibiotics are non-glycosylated heptaketide 14-membered macrolides. These antibiotics exhibit broad-spectrum fungicidal activities, including against the human pathogen Cryptococcus neoformans. Previously, galbonolides B and E were isolated from the marine actinomycete Streptomyces sp. LZ35. By bioinformatics analysis, the putative galbonolide biosynthetic gene cluster, gbn, was identified in the genome of strain LZ35. In order to verify that the core genes (gbnA-E) are sufficient for synthesizing the basic structure of galbonolide as previously proposed, we performed the heterologous expression of gbnA-E in a "clean background" host Streptomyces coelicolor ZM12, in which all the native polyketide synthase genes have been deleted. As expected, the production of galbonolide B (1) was detected in the transformant. To the best of our knowledge, this is the first report that demonstrates the essential role of gbnA-E in the biosynthesis of galbonolides by heterologous expression. This heterologous expression system would be helpful to generate novel galbonolide derivatives by co-overexpression of unusual biosynthesis extender units.

References

Jan 1, 1988·Annals of the New York Academy of Sciences·H AchenbachH Zähner
Dec 1, 1986·The Journal of Antibiotics·U FauthH Achenbach
Nov 20, 1998·The Journal of Antibiotics·J M Sigmund, C F Hirsch
May 16, 1997·The Journal of Organic Chemistry·Bruno TseJames Balkovec
Feb 25, 2003·Proceedings of the National Academy of Sciences of the United States of America·Yi-Qiang ChengBen Shen
Apr 26, 2003·Current Opinion in Chemical Biology·Ben Shen
Dec 20, 2003·Bioorganic & Medicinal Chemistry Letters·Hiroki SakohHajime Morishima
Sep 20, 2005·Biochemical and Biophysical Research Communications·Daniel J FerraroS Ramaswamy
Sep 28, 2005·Organic & Biomolecular Chemistry·James EshelbyAdrian Highton
May 8, 2007·Biochemical and Biophysical Research Communications·Jason J ReddickGregory M Raner
Mar 3, 2010·The Journal of Biological Chemistry·Dusan GoranovicHrvoje Petkovic
Mar 5, 2015·Chembiochem : a European Journal of Chemical Biology·Chao LiuYuemao Shen

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Citations

Jul 20, 2018·Antibiotics·Ewa Maria Musiol-Kroll, Wolfgang Wohlleben
Aug 15, 2019·Microbial Cell Factories·Dipesh DhakalRamesh Prasad Pandey
Mar 12, 2019·Engineering in Life Sciences·Qiyuan ZhaoYunzi Luo

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An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

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An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.