(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 spiroverticillatus: NE
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 MVETSSGSIRGFLDRGVPNWRGVPYGRVGHRFRPPEPVVPVERIDARHWG PVSWQLPIILGQTPSTVSPDATESENCLNLNIWSPDPNPDARRPVLMWLH FGSRAYGSGSTSTNDVWHFAARHDAVVVTANYRIGAWGWLYLGALDPDFK DSANLSMLDQIQALRWVKENVAAFGGDPDNVTLFGLSSGSSDVAALLGAP AAKGLFHKAALYSGAQPPMAEERAARFAEDFLESAGPLAATPADLAQLPN VGLRTIHRRMLKQATSKSHGPAMIRYGPFVDGNVLPRSPLESLEMGLMAD VPLLVSNVTEESGAWDAWNAIDTAYLRAFPEHDQSLPHKEKIDALSELIW VGPAKKLLAAQHKGGAPVWYQQFDYAPSTNWRTVLAYPELANRPVHGADV ACLFLDPEGTVGSDEDRAVGAQDQAALLALARDGRVPWTPWTPESPAPHR IGVPAD
References
Title: Characterization of the tautomycin biosynthetic gene cluster from Streptomyces spiroverticillatus unveiling new insights into dialkylmaleic anhydride and polyketide biosynthesis Li W, Ju J, Rajski SR, Osada H, Shen B Ref: Journal of Biological Chemistry, 283:28607, 2008 : PubMed
Tautomycin (TTM) is a highly potent and specific protein phosphatase inhibitor isolated from Streptomyces spiroverticillatus. The biological activity of TTM makes it an important lead for drug discovery, whereas its spiroketal-containing polyketide chain and rare dialkylmaleic anhydride moiety draw attention to novel biosynthetic chemistries responsible for its production. To elucidate the biosynthetic machinery associated with these novel molecular features, the ttm biosynthetic gene cluster from S. spiroverticillatus was isolated and characterized, and its involvement in TTM biosynthesis was confirmed by gene inactivation and complementation experiments. The ttm cluster was localized to a 86-kb DNA region, consisting of 20 open reading frames that encode three modular type I polyketide synthases (TtmHIJ), one type II thioesterase (TtmT), five proteins for methoxymalonyl-S-acyl carrier protein biosynthesis (Ttm-ABCDE), eight proteins for dialkylmaleic anhydride biosynthesis and regulation (TtmKLMNOPRS), as well as two additional regulatory proteins (TtmF and TtmQ) and one tailoring enzyme (TtmG). A model for TTM biosynthesis is proposed based on functional assignments from sequence analysis, which agrees well with previous feeding experiments, and has been further supported by in vivo gene inactivation experiments. These findings set the stage to fully investigate TTM biosynthesis and to biosynthetically engineer new TTM analogs.
Title: Utilization of the methoxymalonyl-acyl carrier protein biosynthesis locus for cloning of the tautomycin biosynthetic gene cluster from Streptomyces spiroverticillatus Li W, Ju J, Osada H, Shen B Ref: Journal of Bacteriology, 188:4148, 2006 : PubMed
Tautomycin (TTM), a potent protein phosphatase inhibitor, consists of a polyketide chain containing a spiroketal moiety and an acyl chain bearing a dialkylmaleic anhydride structure. PCR using degenerate primers was used to clone genes from Streptomyces spiroverticillatus for formation of the methoxymalonyl-acyl carrier protein. This locus was found to contain five genes (ttmC, ttmA, ttmD, ttmB, and ttmE), one of which was used as a probe to clone the 110-kb TTM biosynthetic gene cluster. The involvement of the ttmA gene in TTM biosynthesis was confirmed by gene inactivation and mutation complementation experiments.
