TY - JOUR
T1 - Linking chemistry and genetics in the growing cyanobactin natural products family
AU - Abou Donia, Mohamed S.
AU - Schmidt, Eric W.
N1 - Funding Information:
We are grateful to W. Gerwick (UCSD) for providing an authentic sample of L. majuscula containing wewakazole. We thank K. Parsawar and C. Nelson for performing FT-MS runs. This work was funded by GM071425 (NIH). E.W.S. is a cofounder and officer in Symbion Discovery, Inc., involved in cyanobactin analoging; however, none of the compounds, methods, or pathways reported here are directly related to any commercial interest or patent.
PY - 2011/4/22
Y1 - 2011/4/22
N2 - Ribosomal peptide natural products are ubiquitous, yet relatively few tools exist to predict structures and clone new pathways. Cyanobactin ribosomal peptides are found in ∼30% of all cyanobacteria, but the connection between gene sequence and structure was not defined, limiting the rapid identification of new compounds and pathways. Here, we report discovery of four orphan cyanobactin gene clusters by genome mining and an additional pathway by targeted cloning, which represented a tyrosine O-prenylating biosynthetic pathway. Genome mining enabled discovery of five cyanobactins, including peptide natural products from Spirulina supplements. A phylogenetic model defined four cyanobactin genotypes, which explain the synthesis of multiple cyanobactin structural classes and help direct pathway cloning and structure prediction efforts. These strategies were applied to DNA isolated from a mixed cyanobacterial bloom containing cyanobactins.
AB - Ribosomal peptide natural products are ubiquitous, yet relatively few tools exist to predict structures and clone new pathways. Cyanobactin ribosomal peptides are found in ∼30% of all cyanobacteria, but the connection between gene sequence and structure was not defined, limiting the rapid identification of new compounds and pathways. Here, we report discovery of four orphan cyanobactin gene clusters by genome mining and an additional pathway by targeted cloning, which represented a tyrosine O-prenylating biosynthetic pathway. Genome mining enabled discovery of five cyanobactins, including peptide natural products from Spirulina supplements. A phylogenetic model defined four cyanobactin genotypes, which explain the synthesis of multiple cyanobactin structural classes and help direct pathway cloning and structure prediction efforts. These strategies were applied to DNA isolated from a mixed cyanobacterial bloom containing cyanobactins.
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U2 - 10.1016/j.chembiol.2011.01.019
DO - 10.1016/j.chembiol.2011.01.019
M3 - Article
C2 - 21513887
AN - SCOPUS:79955401110
SN - 1074-5521
VL - 18
SP - 508
EP - 519
JO - Chemistry and Biology
JF - Chemistry and Biology
IS - 4
ER -