TY - JOUR
T1 - Deciphering Deazapurine Biosynthesis
T2 - Pathway for Pyrrolopyrimidine Nucleosides Toyocamycin and Sangivamycin
AU - McCarty, Reid M.
AU - Bandarian, Vahe
N1 - Funding Information:
The authors thank Robert Lyons of the University of Michigan DNA Sequencing Core for his help and insight on difficult to sequence DNA regions. The authors also acknowledge Alberto Rascón (University of Arizona) for a gift of the E. coli GCH I protein. R.M. acknowledges Science Foundation Arizona for a Graduate Fellowship. Support from the National Institutes of Health is gratefully acknowledged (grant GM 72623 to V.B.). In addition, the research of V.B. is supported in part by a Career Award in Biomedical Sciences from the Burroughs Wellcome Fund.
PY - 2008/8/25
Y1 - 2008/8/25
N2 - Pyrrolopyrimidine nucleosides analogs, collectively referred to as deazapurines, are an important class of structurally diverse compounds found in a wide variety of biological niches. In this report, a cluster of genes from Streptomyces rimosus (ATCC 14673) involved in production of the deazapurine antibiotics sangivamycin and toyocamycin was identified. The cluster includes toyocamycin nitrile hydratase, an enzyme that catalyzes the conversion of toyocamycin to sangivamycin. In addition to this rare nitrile hydratase, the cluster encodes a GTP cyclohydrolase I, linking the biosynthesis of deazapurines to folate biosynthesis, and a set of purine salvage/biosynthesis genes, which presumably convert the guanine moiety from GTP to the adenine-like deazapurine base found in toyocamycin and sangivamycin. The gene cluster presented here could potentially serve as a model to allow identification of deazapurine biosynthetic pathways in other bacterial species.
AB - Pyrrolopyrimidine nucleosides analogs, collectively referred to as deazapurines, are an important class of structurally diverse compounds found in a wide variety of biological niches. In this report, a cluster of genes from Streptomyces rimosus (ATCC 14673) involved in production of the deazapurine antibiotics sangivamycin and toyocamycin was identified. The cluster includes toyocamycin nitrile hydratase, an enzyme that catalyzes the conversion of toyocamycin to sangivamycin. In addition to this rare nitrile hydratase, the cluster encodes a GTP cyclohydrolase I, linking the biosynthesis of deazapurines to folate biosynthesis, and a set of purine salvage/biosynthesis genes, which presumably convert the guanine moiety from GTP to the adenine-like deazapurine base found in toyocamycin and sangivamycin. The gene cluster presented here could potentially serve as a model to allow identification of deazapurine biosynthetic pathways in other bacterial species.
KW - CHEMBIO
UR - http://www.scopus.com/inward/record.url?scp=49449106283&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=49449106283&partnerID=8YFLogxK
U2 - 10.1016/j.chembiol.2008.07.012
DO - 10.1016/j.chembiol.2008.07.012
M3 - Article
C2 - 18721750
AN - SCOPUS:49449106283
SN - 1074-5521
VL - 15
SP - 790
EP - 798
JO - Chemistry and Biology
JF - Chemistry and Biology
IS - 8
ER -