title: An acyltransferase domain of FK506 polyketide synthase recognizing both an acyl carrier protein and coenzyme A as acyl donors to transfer allylmalonyl and ethylmalonyl units.
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 AT4FkbB (the AT domain of the fourth module of FK506 PKS) in transacylation reactions showed that AT4FkbB recognizes both an ACP domain (ACPT csA) and CoA as acyl donors for transfer of a unique allylmalonyl (AM) unit to an acyl acceptor ACP domain (ACP4FkbB), resulting in FK506 production. In addition, AT4FkbB uses CoA as an acyl donor to transfer an unusual ethylmalonyl (EM) unit to ACP4FkbB, resulting in FK520 production, and transfers AM units to non-native ACP acceptors. Characterization of AT4FkbB in self-acylation reactions suggests that AT4FkbB 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 AT4FkbB recognizes two acyl donors for the transfer of different acyl units.
  
  
  METHODS
  Nucleotide sequence data have been submitted to the GenBank database under accession numbers KJ000382 and KJ000383.
authors: College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.|Key Laboratory of Microbial Biochemistry and Metabolism Engineering of Zhejiang Province, Hangzhou, Zhejiang, China.
authors: Hui
authors: H
authors: Jiang
authors: College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
authors: Yue-Yue
authors: YY
authors: Wang
authors: College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
authors: Yuan-Yang
authors: YY
authors: Guo
authors: College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
authors: Jie-Jie
authors: JJ
authors: Shen
authors: College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
authors: Xiao-Sheng
authors: XS
authors: Zhang
authors: College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
authors: Hong-Dou
authors: HD
authors: Luo
authors: College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
authors: Ni-Ni
authors: NN
authors: Ren
authors: College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
authors: Xin-Hang
authors: XH
authors: Jiang
authors: College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.|Key Laboratory of Microbial Biochemistry and Metabolism Engineering of Zhejiang Province, Hangzhou, Zhejiang, China.
authors: Yong-Quan
authors: YQ
authors: Li
mesh_terms: D000213:Acyl Carrier Protein / Q000737:chemistry*; D000217:Acyltransferases / Q000737:chemistry*; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D003065:Coenzyme A / Q000737:chemistry*; D008969:Molecular Sequence Data; D005810:Multigene Family; D048630:Polyketide Synthases / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D013302:Streptomyces / Q000378:metabolism; D013379:Substrate Specificity; D016559:Tacrolimus / Q000378:metabolism*
chemical_list: D000213:Acyl Carrier Protein; D048630:Polyketide Synthases; D000217:Acyltransferases; D003065:Coenzyme A; D016559:Tacrolimus
keywords: acyl carrier protein; acyl donor; acyl unit; acyltransferase; polyketide