A1 Refereed original research article in a scientific journal
Characterization of the Alnumycin Gene Cluster Reveals Unusual Gene Products for Pyran Ring Formation and Dioxan Biosynthesis
Authors: Oja T, Palmu K, Lehmussola H, Lepparanta O, Hannikainen K, Niemi J, Mantsala P, Metsa-Ketela M
Publisher: CELL PRESS
Publication year: 2008
Journal:Chemistry and Biology
Journal name in sourceCHEMISTRY & BIOLOGY
Journal acronym: CHEM BIOL
Volume: 15
Issue: 10
First page : 1046
Last page: 1057
Number of pages: 12
ISSN: 1074-5521
DOI: https://doi.org/10.1016/j.chembiol.2008.07.022
Abstract
Alnumycin is closely related to the benzoisochromanequinone (BIQ) polyketides such as actinorhodin. Exceptional structural features include differences in aglycone tailoring that result in the unique alnumycin chromophore and the existence of an unusual 4-hydroxymethyl-5-hydroxy-1,3-dioxan moiety. Cloning and sequencing of the alnumycin gene cluster from Streptomyces sp. CM020 revealed expected biosynthesis genes for polyketide assembly, but several genes encoding subsequent tailoring enzymes were highly atypical. Heterologous expression studies confirmed that all of the genes required for alnumycin biosynthesis resided within the sequenced clone. Inactivation of genes a1n4 and aln5 showed that the mechanism of pyran ring formation differs from actinorhodin and granaticin pathways. Further inactivation studies identified two genes, alnA and alnB, involved in the synthesis and attachment of the dioxan moiety, and resulted in the production of the polyketide prealnumycin.
Alnumycin is closely related to the benzoisochromanequinone (BIQ) polyketides such as actinorhodin. Exceptional structural features include differences in aglycone tailoring that result in the unique alnumycin chromophore and the existence of an unusual 4-hydroxymethyl-5-hydroxy-1,3-dioxan moiety. Cloning and sequencing of the alnumycin gene cluster from Streptomyces sp. CM020 revealed expected biosynthesis genes for polyketide assembly, but several genes encoding subsequent tailoring enzymes were highly atypical. Heterologous expression studies confirmed that all of the genes required for alnumycin biosynthesis resided within the sequenced clone. Inactivation of genes a1n4 and aln5 showed that the mechanism of pyran ring formation differs from actinorhodin and granaticin pathways. Further inactivation studies identified two genes, alnA and alnB, involved in the synthesis and attachment of the dioxan moiety, and resulted in the production of the polyketide prealnumycin.
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