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Appl. Environ. Microbiol. doi:10.1128/AEM.01308-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Engineering of Primary Carbohydrate Metabolism for Increased Production of Actinorhodin in Streptomyces coelicolor

School of Biological Sciences, Seoul National University, Seoul 151-747, Republic of Korea; Department of Molecular Microbiology, John Innes Centre, Norwich, NR4 7UH, United Kingdom

^* To whom correspondence should be addressed. Email: lkj12345{at}snu.ac.kr.

	Abstract

The objectives of the current studies were to determine the role of key enzymes in central carbon metabolism in the context of increased production of antibiotics in Streptomyces coelicolor. Genes for glucose-6-phosphate dehydrogenase (Zwf) and phosphoglucomutase (Pgm) were deleted, and those for the acetyl-CoA carboxylase (ACCase) were overexpressed. Under the conditions tested, glucose-6-phosphate dehydrogenase encoded by zwf2 plays a more important role than that encoded by zwf1 in determining the carbon flux to actinorhodin (Act), while the function of phosphoglucomutase (Pgm) encoded by SCO7443 is not clearly understood. The pgm-deleted mutant unexpectedly produced abundant glycogen, but was impaired in Act production, the exact reverse of what had been anticipated. Overexpression of the ACCase resulted in more rapid utilization of glucose and sharply increased the efficiency of its conversion to Act. From the current experiments, it is concluded that carbon storage metabolism plays a significant role in precursor supply for Act production, and that manipulation of central carbohydrate metabolism can lead to an increased production of Act in S. coelicolor.

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