Leinamycin biosynthesis revealing unprecedented architectural complexity for a hybrid polyketide synthase and nonribosomal peptide synthetase.
A 135,638 bp DNA region that encompasses the leinamycin (LNM) biosynthetic gene cluster was sequenced from Streptomyces atroolivaceus S-140. The boundaries of the lnm cluster were defined by systematic inactivation of open reading frames within the sequenced region. The lnm cluster spans 61.3 kb of DNA and consists of 27 genes encoding nonribosomal peptide synthetase (NRPS), polyketide synthase (PKS), hybrid NRPS-PKS, resistance, regulatory, and tailoring enzymes, as well as proteins of unknown function. A model for LNM biosynthesis is proposed, central to which is the LNM hybrid NRPS-PKS megasynthetase consisting of discrete (LnmQ and LnmP) and modular (LnmI) NRPS, acyltransferase-less PKS (LnmG, LnmI, and LnmJ), and PKS modules with unusual domain organization. These studies unveil an unprecedented architectural complexity for the LNM hybrid NRPS-PKS megasynthetase and set the stage to investigate the molecular basis for LNM biosynthesis.
Tang
Gong-Li
GL
Division of Pharmaceutical Sciences, University of Wisconsin, Madison, Wisconsin 53705, USA.
Cheng
Yi-Qiang
YQ
Shen
Ben
B
D000595:Amino Acid Sequence; D000903:Antibiotics, Antineoplastic / Q000096:biosynthesis*; D003001:Cloning, Molecular; D005798:Genes, Bacterial; D005809:Genes, Regulator; D007769:Lactams; D018942:Macrolides / Q000378:metabolism*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics*; D005810:Multigene Family; D010453:Peptide Synthases / Q000235:genetics*; D010802:Phylogeny; D016415:Sequence Alignment; D017421:Sequence Analysis; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism*; D013871:Thiones / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D007769:Lactams; D018942:Macrolides; D009097:Multienzyme Complexes; D013844:Thiazoles; D013871:Thiones; C059000:leinamycin; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase