| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Jiang, Hui Wang, Yue-Yue Guo, Yuan-Yang Shen, Jie-Jie Zhang, Xiao-Sheng Luo, Hong-Dou Ren, Ni-Ni Jiang, Xin-Hang Li, Yong-Quan |
| Description |
Country affiliation: China Author Affiliation: Jiang H ( College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.); Wang YY ( Key Laboratory of Microbial Biochemistry and Metabolism Engineering of Zhejiang Province, Hangzhou, Zhejiang, China.); Guo YY ( College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.); Shen JJ ( College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.); Zhang XS ( College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.); Luo HD ( College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.); Ren NN ( College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.); Jiang XH ( College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.); Li YQ ( College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.) |
| Abstract |
Acyltransferase (AT) domains of polyketide synthases (PKSs) usually use coenzyme A (CoA) as an acyl donor to transfer common acyl units to acyl carrier protein (ACP) domains, initiating incorporation of acyl units into polyketides. Two clinical immunosuppressive agents, FK506 and FK520, are biosynthesized by the same PKSs in several Streptomyces strains. In this study, characterization of $AT4_{FkbB}$ (the AT domain of the fourth module of FK506 PKS) in transacylation reactions showed that $AT4_{FkbB}$ recognizes both an ACP domain $(ACP_{TcsA})$ and CoA as acyl donors for transfer of a unique allylmalonyl (AM) unit to an acyl acceptor ACP domain $(ACP4_{FkbB}),$ resulting in FK506 production. In addition, $AT4_{FkbB}$ uses CoA as an acyl donor to transfer an unusual ethylmalonyl (EM) unit to $ACP4_{FkbB},$ resulting in FK520 production, and transfers AM units to non-native ACP acceptors. Characterization of $AT4_{FkbB}$ in self-acylation reactions suggests that $AT4_{FkbB}$ controls acyl unit specificity in transacylation reactions but not in self-acylation reactions. Generally, AT domains of PKSs only recognize one acyl donor; however, we report here that $AT4_{FkbB}$ recognizes two acyl donors for the transfer of different acyl units. |
| File Format |
HTM / HTML |
| ISSN |
1742464X |
| Issue Number |
13 |
| Volume Number |
282 |
| e-ISSN |
17424658 |
| Journal |
FEBS Journal |
| Language |
English |
| Publisher |
Wiley (on behalf of the Federation of European Biochemical Societies) |
| Publisher Date |
2015-07-01 |
| Publisher Place |
Great Britain (UK) |
| Access Restriction |
One Nation One Subscription (ONOS) |
| Subject Keyword |
Discipline Biochemistry Acyl Carrier Protein Chemistry Acyltransferases Coenzyme A Polyketide Synthases Tacrolimus Metabolism Base Sequence Chromatography, High Pressure Liquid Molecular Sequence Data Multigene Family Protein Structure, Tertiary Streptomyces Substrate Specificity Journal Article Research Support, Non-u.s. Gov't |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Cell Biology Biochemistry Molecular Biology |
