A streamlined metabolic pathway for the biosynthesis of moenomycin A.
Moenomycin A (MmA) is a member of the phosphoglycolipid family of antibiotics, which are the only natural products known to directly target the extracellular peptidoglycan glycosyltransferases involved in bacterial cell wall biosynthesis. The structural and biological uniqueness of MmA make it an attractive starting point for the development of new antibacterial drugs. In order both to elucidate the biosynthesis of this unusual compound and to develop tools to manipulate its structure, we have identified the MmA biosynthetic genes in Streptomyces ghanaensis (ATCC14672). We show via heterologous expression of a subset of moe genes that the economy of the MmA pathway is enabled through the use of sugar-nucleotide and isoprenoid building blocks derived from primary metabolism. The work reported lays the foundation for genetic engineering of MmA biosynthesis to produce novel derivatives.
Ostash
Bohdan
B
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.
Saghatelian
Alan
A
Walker
Suzanne
S
D001409:Bacillus cereus / Q000201:enzymology / Q000235:genetics; D001426:Bacterial Proteins / Q000378:metabolism; D001455:Bambermycins / Q000096:biosynthesis* / Q000737:chemistry; D002240:Carbohydrate Sequence; D004269:DNA, Bacterial / Q000235:genetics / Q000302:isolation & purification; D016695:Glycosyltransferases / Q000378:metabolism; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D013302:Streptomyces / Q000201:enzymology* / Q000235:genetics; D014158:Transcription, Genetic
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D001455:Bambermycins; C437243:moenomycin A; D016695:Glycosyltransferases