The biosynthetic gene cluster for the beta-lactam carbapenem thienamycin in Streptomyces cattleya.
beta-lactam ring formation in carbapenem and clavam biosynthesis proceeds through an alternative mechanism to the biosynthetic pathway of classic beta-lactam antibiotics. This involves the participation of a beta-lactam synthetase. Using available information from beta-lactam synthetases, we generated a probe for the isolation of the thienamycin cluster from Streptomyces cattleya. Genes homologous to carbapenem and clavulanic acid biosynthetic genes have been identified. They would participate in early steps of thienamycin biosynthesis leading to the formation of the beta-lactam ring. Other genes necessary for the biosynthesis of thienamycin have also been identified in the cluster (methyltransferases, cysteinyl transferases, oxidoreductases, hydroxylase, etc.) together with two regulatory genes, genes involved in exportation and/or resistance, and a quorum sensing system. Involvement of the cluster in thienamycin biosynthesis was demonstrated by insertional inactivation of several genes generating thienamycin nonproducing mutants.
Departamento de Biología Funcional and Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, 33006 Oviedo, Spain.
Luz Elena
LE
Núñez
Carmen
C
Méndez
Alfredo F
AF
Braña
Gloria
G
Blanco
José A
JA
Salas
D000595:Amino Acid Sequence; D001483:Base Sequence; D002513:Cephamycins / Q000096:biosynthesis; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D004251:DNA Transposable Elements / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D005822:Genetic Vectors; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D009154:Mutation / Q000502:physiology; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism*; D013845:Thienamycins / Q000096:biosynthesis*
D002513:Cephamycins; D004251:DNA Transposable Elements; D004269:DNA, Bacterial; D013845:Thienamycins; C024925:cephamycin C