Document Detail


Mechanism of the incidental production of a melanin-like pigment during 6-demethylchlortetracycline production in Streptomyces aureofaciens.
MedLine Citation:
PMID:  10742218     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The secondary metabolite 6-demethylchlortetracycline (6-DCT), which is produced by Streptomyces aureofaciens, is used as a precursor of semisynthetic tetracyclines. Strains that produce 6-DCT also produce a melanin-like pigment (MP). The correlation between MP production and 6-DCT production was investigated by using S. aureofaciens NRRL 3203. Production of both MP and 6-DCT was repressed by phosphate or ammonium ions, suggesting that syntheses of these compounds are controlled by the same regulators. Ten chlortetracycline-producing recombinants were derived from 6-DCT-producing mutant NRRL 3203 by gene replacement. All of the recombinants produced chlortetracycline but not MP, indicating that MP production is the results of a defect in the 6-methylation step and suggesting that the polyketide nonaketideamide is a common intermediate leading to MP as well as 6-DCT. To further examine the possibility that MP might be synthesized via the 6-DCT-biosynthetic pathway, mutants defective in 6-DCT biosynthesis were derived from a 6-DCT producer. Some of these mutants were able to produce MP, while others, including mutants with mutations in the gene encoding anhydrotetracycline oxygenase, an enzyme catalyzing the penultimate step in the pathway, produced neither 6-DCT nor MP. Production of 6-DCT and production of MP were restored simultaneously by integrative transformation with the corresponding 6-DCT-biosynthetic genes, indicating that some of 6-DCT-biosynthetic enzymes are indispensable for MP production. These findings suggest that a defect in the 6-methylation step results in redirection of carbon flux from a certain intermediate in the 6-DCT-biosynthetic pathway to a shunt pathway and results in MP production.
Authors:
T Nakano; K Miyake; M Ikeda; T Mizukami; R Katsumata
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Applied and environmental microbiology     Volume:  66     ISSN:  0099-2240     ISO Abbreviation:  Appl. Environ. Microbiol.     Publication Date:  2000 Apr 
Date Detail:
Created Date:  2000-05-11     Completed Date:  2000-05-11     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7605801     Medline TA:  Appl Environ Microbiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1400-4     Citation Subset:  IM    
Affiliation:
Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Machida, Tokyo 194-8533, Japan. t.nakano@kyowa.co.jp
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MeSH Terms
Descriptor/Qualifier:
Anti-Bacterial Agents / biosynthesis*
Culture Media
Demeclocycline / biosynthesis*
Gene Expression Regulation, Bacterial
Melanins / biosynthesis*
Methylation
Multigene Family
Mutation
Pigments, Biological / biosynthesis*
Plasmids / genetics
Recombination, Genetic
Streptomyces aureofaciens / genetics,  growth & development,  metabolism*
Chemical
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Culture Media; 0/Melanins; 0/Pigments, Biological; 127-33-3/Demeclocycline
Comments/Corrections

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