Complete genome sequence of the rifamycin SV-producing Amycolatopsis mediterranei U32 revealed its genetic characteristics in phylogeny and metabolism.
Amycolatopsis mediterranei is used for industry-scale production of rifamycin, which plays a vital role in antimycobacterial 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 'quasi-core' 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.
Zhao
Wei
W
Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China.
Zhong
Yi
Y
Yuan
Hua
H
Wang
Jin
J
Zheng
Huajun
H
Wang
Ying
Y
Cen
Xufeng
X
Xu
Feng
F
Bai
Jie
J
Han
Xiaobiao
X
Lu
Gang
G
Zhu
Yongqiang
Y
Shao
Zhihui
Z
Yan
Han
H
Li
Chen
C
Peng
Nanqiu
N
Zhang
Zilong
Z
Zhang
Yunyi
Y
Lin
Wei
W
Fan
Yun
Y
Qin
Zhongjun
Z
Hu
Yongfei
Y
Zhu
Baoli
B
Wang
Shengyue
S
Ding
Xiaoming
X
Zhao
Guo-Ping
GP
D000192:Actinomycetales / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D002244:Carbon / Q000378:metabolism; D016680:Genome, Bacterial; D053858:Metabolic Networks and Pathways; D005810:Multigene Family; D009584:Nitrogen / Q000378:metabolism; D010802:Phylogeny; D012294:Rifamycins / Q000096:biosynthesis*
D000900:Anti-Bacterial Agents; D012294:Rifamycins; D002244:Carbon; C023808:rifamycin SV; D009584:Nitrogen