TY - JOUR
T1 - Bleomycin biosynthesis in Streptomyces verticillus ATCC15003
T2 - A model of hybrid peptide and polyketide biosynthesis
AU - Shen, Ben
AU - Du, Liangcheng
AU - Sanchez, Cesar
AU - Chen, Meim
AU - Edwards, Daniel J.
N1 - Funding Information:
We thank Michael Calcutt and Frank Schmidt, University of Missouri-Columbia, for clones of the blmAB locus; Dr. Tomohisa Takita, Institute of Microbial Chemistry, Microbial Chemistry Research Foundation, Japan, for authentic samples of 4 and 13; and Professor C. Richard Hutchinson, University of Wisconsin, Madison, for helpful discussion and constant encouragement. This work was supported in part by an Institutional Research Grant from the American Cancer Society and the School of Medicine, University of California, Davis; the National Institutes of Health Grant AI40475; and the Searle Scholars Program/The Chicago Community Trust.
PY - 1999/4
Y1 - 1999/4
N2 - The biosynthesis of bleomycins (BLMs) in Streptomyces verticillus (Sv) ATCC15003 was reviewed. Early biosynthetic studies by incorporation of isotope-labeled precursors and by isolation of biosynthetic intermediates and shunt metabolites were presented to support the hypothesis that (a) BLM is a hybrid peptide and polyketide metabolite and (b) the blm synthetase, which catalyzes the assembly of BLM from nine amino acids and an acetate, should bear the characteristics of both nonribosomal peptide synthetase (PTS) and polyketide synthase (PKS). After brief discussion of the cloning and characterization of the blm resistance genes from Sv ATCCI5003 as well as from other microorganisms, emphasis was placed on our current efforts to clone the blm biosynthesis gene cluster from Sv ATCC15003. Four cloning strategies were discussed that included chromosomal walking from the blmAB resistance genes, cloning putative PKS genes by polymerase chain reaction (PCR), cloning putative PTS genes by PCR, and the combination of chromosomal walking from the blm resistance locus and heterologous probing with PTS probes. While at least three additional peptide and one polyketide biosynthesis gene clusters were identified from Sv ATCCI5003, a putative 110- kb blm gene cluster has been cloned. Sequence analysis of 75 kb DNA provided strong support that the cloned gene cluster is responsible for BLM production.
AB - The biosynthesis of bleomycins (BLMs) in Streptomyces verticillus (Sv) ATCC15003 was reviewed. Early biosynthetic studies by incorporation of isotope-labeled precursors and by isolation of biosynthetic intermediates and shunt metabolites were presented to support the hypothesis that (a) BLM is a hybrid peptide and polyketide metabolite and (b) the blm synthetase, which catalyzes the assembly of BLM from nine amino acids and an acetate, should bear the characteristics of both nonribosomal peptide synthetase (PTS) and polyketide synthase (PKS). After brief discussion of the cloning and characterization of the blm resistance genes from Sv ATCCI5003 as well as from other microorganisms, emphasis was placed on our current efforts to clone the blm biosynthesis gene cluster from Sv ATCC15003. Four cloning strategies were discussed that included chromosomal walking from the blmAB resistance genes, cloning putative PKS genes by polymerase chain reaction (PCR), cloning putative PTS genes by PCR, and the combination of chromosomal walking from the blm resistance locus and heterologous probing with PTS probes. While at least three additional peptide and one polyketide biosynthesis gene clusters were identified from Sv ATCCI5003, a putative 110- kb blm gene cluster has been cloned. Sequence analysis of 75 kb DNA provided strong support that the cloned gene cluster is responsible for BLM production.
UR - http://www.scopus.com/inward/record.url?scp=0032830741&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032830741&partnerID=8YFLogxK
U2 - 10.1006/bioo.1998.1131
DO - 10.1006/bioo.1998.1131
M3 - Article
AN - SCOPUS:0032830741
SN - 0045-2068
VL - 27
SP - 155
EP - 171
JO - Bioorganic Chemistry
JF - Bioorganic Chemistry
IS - 2
ER -