Domain Characterization of Cyclosporin Regio-Specific Hydroxylases in Rare Actinomycetes | |
Woo, Min-Woo1; Lee, Bo-Ram1; Nah, Hee-Ju1; Choi, Si-Sun1; Li, Shengying2; Kim, Eung-Soo1 | |
2015-10-01 | |
发表期刊 | JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY |
卷号 | 25期号:10页码:1634-1639 |
摘要 | Cytochrome P450 hydroxylase (CYP) in actinomycetes plays an important role in the biosynthesis and bioconversion of various secondary metabolites. Two unique CYPs named CYP-sb21 and CYP-pa1, which were identified from Sebekia benihana and Pseudonocardia autotrophica, respectively, were proven to transfer a hydroxyl group at the 4th or 9th N-methyl leucine position of immunosuppressive agent cyclosporin A (CsA). Interestingly, these two homologous CYPs showed different CsA regio-selectivities. CYP-sb21 exhibited preferential hydroxylation activity at the 4th position over the 9th position, whereas CYP-pa1 showed the opposite preference. To narrow down the CYP domain critical for CsA regio-selectivity, each CYP was divided into four domains, and each domain was swapped with its counterpart from the other CYP. A total of 18 hybrid CYPs were then individually tested for CsA regioselectivity. Although most of the hybrid CYPs failed to exhibit a significant change in regioselectivity in the context of CsA hydroxylation, hybrid CYP-pa1 swapped with the second domain of CYP-sb21 showed a higher preference for the 9th position. Moreover, hybrid CYP-sb21 containing seven amino acids from the 2nd domain of CYP-pa1 showed higher preference for the 4th position. These results imply that the 2nd domain of CsA-specific CYP plays a critical role in CsA regio-selectivity, thereby setting the stage for biotechnological application of CsA regio-selective hydroxylation. |
文章类型 | Article |
关键词 | Cytochrome P450 Cyclosporin a Regio-selectivity Actinomycetes |
WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
DOI | 10.4014/jmb.1505.05034 |
关键词[WOS] | CYTOCHROME-P450 COMPLEMENT CYPOME ; SEBEKIA-BENIHANA ; FERREDOXIN REDUCTASE ; STREPTOMYCES ; GENE ; DISRUPTION ; CONVERSION ; BINDING |
收录类别 | SCI |
语种 | 英语 |
WOS研究方向 | Biotechnology & Applied Microbiology ; Microbiology |
项目资助者 | National Research Foundation of Korea (NRF) - Korea government (MSIP)(NRF-2014R1A2A1A11052236) |
WOS类目 | Biotechnology & Applied Microbiology ; Microbiology |
WOS记录号 | WOS:000365443800008 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://ir.qibebt.ac.cn/handle/337004/6799 |
专题 | 酶工程研究组 |
作者单位 | 1.Inha Univ, Dept Biol Engn, Inchon 402751, South Korea 2.Chinese Acad Sci, Qingdao Inst Bioenergy & Bioproc Technol, Qingdao 266101, Shandong, Peoples R China |
推荐引用方式 GB/T 7714 | Woo, Min-Woo,Lee, Bo-Ram,Nah, Hee-Ju,et al. Domain Characterization of Cyclosporin Regio-Specific Hydroxylases in Rare Actinomycetes[J]. JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY,2015,25(10):1634-1639. |
APA | Woo, Min-Woo,Lee, Bo-Ram,Nah, Hee-Ju,Choi, Si-Sun,Li, Shengying,&Kim, Eung-Soo.(2015).Domain Characterization of Cyclosporin Regio-Specific Hydroxylases in Rare Actinomycetes.JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY,25(10),1634-1639. |
MLA | Woo, Min-Woo,et al."Domain Characterization of Cyclosporin Regio-Specific Hydroxylases in Rare Actinomycetes".JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY 25.10(2015):1634-1639. |
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