(Below N is a link to NCBI taxonomic web page and E link to ESTHER at designed phylum.) > cellular organisms: NE > Bacteria: NE > Terrabacteria group: NE > Actinobacteria [phylum]: NE > Actinobacteria [class]: NE > Streptomycetales: NE > Streptomycetaceae: NE > Streptomyces: NE > Streptomyces sp. CK4412: NE
Warning: This entry is a compilation of different species or line or strain with more than 90% amino acide identity. You can retrieve all strain data
(Below N is a link to NCBI taxonomic web page and E link to ESTHER at designed phylum.) Streptomyces griseochromogenes: N, E.
LegendThis sequence has been compared to family alignement (MSA) red => minority aminoacid blue => majority aminoacid color intensity => conservation rate title => sequence position(MSA position)aminoacid rate Catalytic site Catalytic site in the MSA MKPPALVVPGPVPPWNYRRGSRPTRPRLRELTAMGDHFDRDLVVETSSGT VRGFLDRGTPNWRGVPYGRVEQRFHPPVPALPGEPVDGRHWGPICWQLPI VAGRSPSSVFPDAAESEDCLNLNVWSPGPDPGARRPVLVWLHFGSRAYGA GSTPMIDVWHFAARHNAVVVTPNYRLGPWGWLYLGALDPEFEDSANLALL DQILMLRWVKDNIAAFGGDPDNVTVFGMSSGASDLGALLGAPAARGLFHK AASYSGAQAPMLEKDATEFAEEFLAAAGPLAATAAELAALPNVGLRTVHR RLLKQSVSRAGGPIIIRYGPFVDGSVLPKAPLDALADGLMAGVALLVSNV AEEAGVWDAWGAVDHAYSRVFAGSDQSVSHEEKVEQLSEYRWVGPARKLI AAHHQGGGTGWMQKFDYAPTTNWQTALSYPEVARRPVHGADVASLFLDPE GEVGSEDDRAVAALDQAALLALARDGRAPWTPWSPDNQTPHRIAAAAH
References
Title: Characterization of the tautomycetin biosynthetic gene cluster from Streptomyces griseochromogenes provides new insight into dialkylmaleic anhydride biosynthesis Li W, Luo Y, Ju J, Rajski SR, Osada H, Shen B Ref: Journal of Natural Products, 72:450, 2009 : PubMed
Tautomycetin (TTN) is a highly potent and specific protein phosphatase inhibitor isolated from Streptomyces griseochromogenes. The biological activity of TTN makes it an important lead for drug discovery, whereas its rare dialkylmaleic anhydride moiety and structural similarity to tautomycin (TTM), another potent phosphatase inhibitor with tremendous medicinal potential, draws attention to novel biosynthetic chemistries responsible for its production. To elucidate the biosynthetic machinery associated with TTN production, the ttn biosynthetic gene cluster from S. griseochromogenes was isolated and characterized, and its involvement in TTN biosynthesis confirmed by gene inactivation and complementation experiments. The ttn cluster was localized to a 79 kb DNA region, consisting of 19 open reading frames that encode two modular type I polyketide synthases (TtnAB), one type II thioesterase (TtnH), eight proteins for dialkylmaleic anhydride biosynthesis (TtnKLMNOPRS), four tailoring enzymes (TtnCDFI), two regulatory proteins (TtnGQ), and one resistance protein (TtnJ). A model for TTN biosynthesis is proposed on the basis of functional assignments from sequence analysis, which agrees well with previous feeding experiments, has been supported by in vivo gene inactivation experiments, and is supported by analogy to the recently reported ttm cluster. These findings set the stage to fully investigate TTN biosynthesis and to biosynthetically engineer new TTN analogues.
Title: Isolation of the biosynthetic gene cluster for tautomycetin, a linear polyketide T cell-specific immunomodulator from Streptomyces sp. CK4412 Choi SS, Hur YA, Sherman DH, Kim ES Ref: Microbiology, 153:1095, 2007 : PubMed
The bacterial genus Streptomyces has long been appreciated for its ability to produce various kinds of medically important secondary metabolites, such as antibiotics, anti-tumour agents, immunosuppressants and enzyme inhibitors. Tautomycetin (TMC), which is produced by Streptomyces sp. CK4412, is a novel activated T cell-specific immunosuppressive compound with an ester bond linkage between a terminal cyclic anhydride moiety and a linear polyketide chain bearing an unusual terminal alkene. Using a Streptomyces polyketide methylmalonyl-CoA acyltransferase gene as a probe, three overlapping cosmids were isolated from the genomic library of TMC-producing Streptomyces sp. CK4412. Sequence information of an approximately 70 kb contiguous DNA region revealed two multi-modular type I polyketide synthases (PKSs), and 12 additional gene products presumably involved in TMC biosynthesis. The deduced roles for most of the TMC PKS catalytic domains were consistent with the expected functions necessary for TMC chain elongation and processing. In addition, disruption of a putative TMC acyl-CoA transferase gene, located upstream of the PKS gene locus, completely abolished TMC biosynthesis. Taken together, these data provide strong supporting evidence that the cloned gene cluster identified in this study is responsible for TMC biosynthesis in Streptomyces sp. CK4412, and set the stage for detailed genetic and biochemical studies of the biosynthesis of this important metabolite.
