Amycolatopsis mediterranei is used for industry-scale production of rifamycin, which plays a vital role in antimyco- bacterial therapy. As the first sequenced genome of the genus Amycolatopsis, the chromosome of strai...Amycolatopsis mediterranei is used for industry-scale production of rifamycin, which plays a vital role in antimyco- bacterial therapy. As the first sequenced genome of the genus Amycolatopsis, the chromosome of strain U32 comprising 10 236 715 base pairs, is one of the largest prokaryotic genomes ever sequenced so far. Unlike the linear topology found in streptomycetes, this chromosome is circular, particularly similar to that of Saccharopolyspora erythraea and Nocardia farcinica, representing their close relationship in phylogeny and taxonomy. Although the predicted 9 228 protein-coding genes in the A. mediterranei genome shared the greatest number of orthologs with those of S. erythraea, it was unexpectedly followed by Streptomyces coelicolor rather than N. farcinica, indicating the distinct metabolic characteristics evolved via adaptation to diverse ecological niches. Besides a core region analogous to that common in streptomycetes, a novel ＇quasicore＇ with typical core characteristics is defined within the non-core region, where 21 out of the total 26 gene clusters for secondary metabolite production are located. The rifamycin biosynthesis gene cluster located in the core encodes a cytochrome P450 enzyme essential for the conversion of rifamycin SV to B, revealed by comparing to the highly homologous cluster of the rifamycin B-producing strain S699 and further confirmed by genetic complementation. The genomic information of A. mediterranei demonstrates a metabolic network orchestrated not only for extensive utilization of various carbon sources and inorganic nitrogen compounds but also for effective funneling of metabolic intermediates into the secondary antibiotic synthesis process under the control of a seemingly complex regulatory mechanism.展开更多
The complete genome of methanol-utilizing Amycolatopsis methanolica strain 239T was generated,revealing a single 7,237,391 nucleotide circular chromosome with 7074 annotated protein-coding sequences(CDSs).Comparative ...The complete genome of methanol-utilizing Amycolatopsis methanolica strain 239T was generated,revealing a single 7,237,391 nucleotide circular chromosome with 7074 annotated protein-coding sequences(CDSs).Comparative analyses against the complete genome sequences of Amycolatopsis japonica strain MG417-CF17T,Amycolatopsis mediterranei strain U32 and Amycolatopsis orientalis strain HCCB10007 revealed a broad spectrum of genomic structures,including various genome sizes,core/quasi-core/non-core configurations and different kinds of episomes.Although polyketide synthase gene clusters were absent from the A.methanolica genome,12 gene clusters related to the biosynthesis of other specialized(secondary)metabolites were identified.Complete pathways attributable to the facultative methylotrophic physiology of A.methanolica strain 239T,including both the mdo/mscR encoded methanol oxidation and the hps/hpi encoded formaldehyde assimilation via the ribulose monophosphate cycle,were identified together with evidence that the latter might be the result of horizontal gene transfer.Phylogenetic analyses based on 16S rDNA or orthologues of AMETH_3452,a novel actinobacterial class-specific conserved gene against 62 or 18 Amycolatopsis type strains,respectively,revealed three major phyletic lineages,namely the mesophilic or moderately thermophilic A.orientalis subclade(AOS),the mesophilic Amycolatopsis taiwanensis subclade(ATS)and the thermophilic A.methanolica subclade(AMS).The distinct growth temperatures of members of the subclades correlated with corresponding genetic variations in their encoded compatible solutes.This study shows the value of integrating conventional taxonomic with whole genome sequence data.展开更多
基金This paper is dedicated to the late Professor JS Chiao, who initiated the research in China for rifamycin production employing A. mediterranei more than 30 years ago and who continued the endeavor to resolve the mechanism of the ＇nitrate stimulating effect＇ up to the last breath of his life. This work was supported by the National Natural Science Foundation of China （30830002）, the National High Technology Research and Development Program of China （2007AA021301, 2007AA021503）, and the Research Unit Fund of Li Ka Shing Institute of Health Sciences （7103506）.
文摘Amycolatopsis mediterranei is used for industry-scale production of rifamycin, which plays a vital role in antimyco- bacterial therapy. As the first sequenced genome of the genus Amycolatopsis, the chromosome of strain U32 comprising 10 236 715 base pairs, is one of the largest prokaryotic genomes ever sequenced so far. Unlike the linear topology found in streptomycetes, this chromosome is circular, particularly similar to that of Saccharopolyspora erythraea and Nocardia farcinica, representing their close relationship in phylogeny and taxonomy. Although the predicted 9 228 protein-coding genes in the A. mediterranei genome shared the greatest number of orthologs with those of S. erythraea, it was unexpectedly followed by Streptomyces coelicolor rather than N. farcinica, indicating the distinct metabolic characteristics evolved via adaptation to diverse ecological niches. Besides a core region analogous to that common in streptomycetes, a novel ＇quasicore＇ with typical core characteristics is defined within the non-core region, where 21 out of the total 26 gene clusters for secondary metabolite production are located. The rifamycin biosynthesis gene cluster located in the core encodes a cytochrome P450 enzyme essential for the conversion of rifamycin SV to B, revealed by comparing to the highly homologous cluster of the rifamycin B-producing strain S699 and further confirmed by genetic complementation. The genomic information of A. mediterranei demonstrates a metabolic network orchestrated not only for extensive utilization of various carbon sources and inorganic nitrogen compounds but also for effective funneling of metabolic intermediates into the secondary antibiotic synthesis process under the control of a seemingly complex regulatory mechanism.
基金This work was supported in part by grants from the National Basic Research Program of China(2012CB721102,2013CB734000)the Natural Science Foundation for Youth(31300034)+1 种基金the National Natural Science Foundation of China(31270056,31430004 and 31421061)LX.Z.is an Awardee of the National Distinguished Young Scholar Program in China(31125002).
文摘The complete genome of methanol-utilizing Amycolatopsis methanolica strain 239T was generated,revealing a single 7,237,391 nucleotide circular chromosome with 7074 annotated protein-coding sequences(CDSs).Comparative analyses against the complete genome sequences of Amycolatopsis japonica strain MG417-CF17T,Amycolatopsis mediterranei strain U32 and Amycolatopsis orientalis strain HCCB10007 revealed a broad spectrum of genomic structures,including various genome sizes,core/quasi-core/non-core configurations and different kinds of episomes.Although polyketide synthase gene clusters were absent from the A.methanolica genome,12 gene clusters related to the biosynthesis of other specialized(secondary)metabolites were identified.Complete pathways attributable to the facultative methylotrophic physiology of A.methanolica strain 239T,including both the mdo/mscR encoded methanol oxidation and the hps/hpi encoded formaldehyde assimilation via the ribulose monophosphate cycle,were identified together with evidence that the latter might be the result of horizontal gene transfer.Phylogenetic analyses based on 16S rDNA or orthologues of AMETH_3452,a novel actinobacterial class-specific conserved gene against 62 or 18 Amycolatopsis type strains,respectively,revealed three major phyletic lineages,namely the mesophilic or moderately thermophilic A.orientalis subclade(AOS),the mesophilic Amycolatopsis taiwanensis subclade(ATS)and the thermophilic A.methanolica subclade(AMS).The distinct growth temperatures of members of the subclades correlated with corresponding genetic variations in their encoded compatible solutes.This study shows the value of integrating conventional taxonomic with whole genome sequence data.
