Cloning and characterization of the ravidomycin and chrysomycin biosynthetic gene clusters.
Cloning and characterization of the ravidomycin and chrysomycin biosynthetic gene clusters.
复制标题
DOI：
10.1002/cbic.200900673
复制
发表时间：
2010-03-01
期刊：
影响因子：
3.2
通讯作者：
Rohr, Juergen
中科院分区：
文献类型：
--
作者：
Kharel, Madan K.;Nybo, S. Eric;Shepherd, Micah D.;Rohr, Juergen
从链霉菌中分别克隆了两种抗肿瘤抗生素雷维多霉素和金霉素的生物合成基因簇。对cosRav 32的33.28 kb DNA区域和cosChry 1 -1和cosChryF 2的34.65 kb DNA区域进行测序，分别揭示了36和35个开放阅读框（ORF），含有串联的II型聚酮合酶（PKS）基因、d-雷维糖胺和d-病毒糖生物合成基因、PKS后剪裁基因、调节基因和未知功能的基因。分离的雷维多霉素基因簇被证实参与雷维多霉素的生物合成，通过在变铅青链霉菌TK 24中异源表达粘粒cosRav 32后产生新的雷维多霉素类似物沿着预期的途径中间体和生物合成分流产物。通过gilvocarcin V（GV）突变体的交叉互补进一步验证了簇的身份。类似地，金霉素基因簇被证明是间接参与金霉素生物合成，通过交叉互补的gilvocarcin突变体缺乏的加氧酶GilOII，GilOIII，和GilOIV与各自的金霉素单加氧酶同系物。雷维多霉素糖基转移酶（RavGT）似乎能够将氨基糖和中性糖（通过结构上不同的6元d-雷维多胺和5元d-岩藻呋喃糖举例说明）转移至香豆素基聚酮衍生的主链。这些结果扩展了参与gilvocarcin类化合物的生物合成的生物合成基因的文库，所述gilvocarcin类化合物可用于通过组合生物合成产生新的类似物。
The gene clusters responsible for the biosynthesis of two anti-tumor antibiotics, ravidomycin and chrysomycin, have been cloned from Streptomyces ravidus and Streptomyces albaduncus, respectively. Sequencing of the 33.28 kb DNA region of the cosmid cosRav32 and the 34.65 kb DNA region of cosChry1-1 and cosChryF2 revealed 36 and 35 open reading frames (ORFs), respectively, harboring tandem sets of type II polyketide synthase (PKS) genes, d-ravidosamine and d-virenose biosynthetic genes, post-PKS tailoring genes, regulatory genes, and genes of unknown function. The isolated ravidomycin gene cluster was confirmed to be involved in ravidomycin biosynthesis through the production of a new analogue of ravidomycin along with anticipated pathway intermediates and biosynthetic shunt products upon heterologous expression of the cosmid, cosRav32, in Streptomyces lividans TK24. The identity of the cluster was further verified through cross complementation of gilvocarcin V (GV) mutants. Similarly, the chrysomycin gene cluster was demonstrated to be indirectly involved in chrysomycin biosynthesis through cross-complementation of gilvocarcin mutants deficient in the oxygenases GilOII, GilOIII, and GilOIV with the respective chrysomycin monooxygenase homologues. The ravidomycin glycosyltransferase (RavGT) appears to be able to transfer both amino- and neutral sugars, exemplified through the structurally distinct 6-membered d-ravidosamine and 5-membered d-fucofuranose, to the coumarin-based polyketide derived backbone. These results expand the library of biosynthetic genes involved in the biosyntheses of gilvocarcin class compounds that can be used to generate novel analogues through combinatorial biosynthesis.
登录
查看更多内容
影响因子：
2.9
作者：
Burgie, E. Sethe;Holden, Hazel M.
通讯作者：
Holden, Hazel M.
结构化钙钛矿薄膜的受控生长用于高性能太阳能电池
影响因子：
17.6
作者：
Fei, Chengbin;Guo, Lixue;Cao, Guozhong
通讯作者：
Cao, Guozhong
影响因子：
3.5
作者：
BIBB, MJ;SHERMAN, DH;HOPWOOD, DA
通讯作者：
HOPWOOD, DA
影响因子：
5.1
作者：
Crawford, Jason M.;Vagstad, Anna L.;Townsend, Craig A.
通讯作者：
Townsend, Craig A.
影响因子：
1.8
作者：
Futagami, S;Ohashi, Y;Suzuki, K
通讯作者：
Suzuki, K