title: fabC of Streptomyces lydicus involvement in the biosynthesis of streptolydigin.
abstract: Streptolydigin, a secondary metabolite produced by Streptomyces lydicus, is a potent inhibitor of bacterial RNA polymerases. It has been suggested that streptolydigin biosynthesis is associated with polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS). Thus, there is great interest in understanding the role of fatty acid biosynthesis in the biosynthesis of streptolydigin. In this paper, we cloned a type II fatty acid synthase (FAS II) gene cluster of fabDHCF from the genome of S. lydicus and constructed the SlyfabCF-disrupted mutant. Sequence analysis showed that SlyfabDHCF is 3.7 kb in length and encodes four separated proteins with conserved motifs and active residues, as shown in the FAS II of other bacteria. The SlyfabCF disruption inhibited streptolydigin biosynthesis and retarded mycelial growth, which were likely caused by the inhibition of fatty acid synthesis. Streptolydigin was not detected in the culture of the mutant strain by liquid chromatography-mass spectrometry. Meanwhile, the streptolol moiety of streptolydigin accumulated in cultures. As encoded by fabCF, acyl carrier protein (ACP) and beta-ketoacyl-ACP synthase II are required for streptolydigin biosynthesis and likely involved in the step between PKS and NRPS. Our results provide the first genetic and metabolic evidence that SlyfabCF is shared by fatty acid synthesis and antibiotic streptolydigin synthesis.
authors.affiliation: Key Laboratory of Systems Bioengineering, Ministry of Education, Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, P.O. Box 6888, People's Republic of China. grzhao@tju.edu.cn
authors.forename: Guang-Rong
authors.initials: GR
authors.lastname: Zhao
authors.forename: Ting
authors.initials: T
authors.lastname: Luo
authors.forename: Yong-Jin
authors.initials: YJ
authors.lastname: Zhou
authors.forename: Xin
authors.initials: X
authors.lastname: Jiang
authors.forename: Bin
authors.initials: B
authors.lastname: Qiao
authors.forename: Feng-Ming
authors.initials: FM
authors.lastname: Yu
authors.forename: Ying-Jin
authors.initials: YJ
authors.lastname: Yuan
mesh_terms: D000617:Aminoglycosides / Q000096:biosynthesis* / Q000737:chemistry; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D054889:Fatty Acid Synthase, Type II / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009876:Operon; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*
chemical_list: D000617:Aminoglycosides; D001426:Bacterial Proteins; C100307:streptolydigin; D054889:Fatty Acid Synthase, Type II