An acyltransferase domain of FK506 polyketide synthase recognizing both an acyl carrier protein and coenzymeA as acyl donors to transfer allylmalonyl and ethylmalonyl units
An acyltransferase domain of FK506 polyketide synthase recognizing both an acyl carrier protein and coenzymeA as acyl donors to transfer allylmalonyl and ethylmalonyl units
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FK506 聚酮合酶的酰基转移酶结构域识别酰基载体蛋白和辅酶 A 作为酰基供体以转移烯丙基丙二酰基和乙基丙二酰基单位
DOI：
10.1111/febs.13296
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发表时间：
2015-07-01
期刊：
影响因子：
5.4
通讯作者：
Li, Yong-Quan
中科院分区：
文献类型：
--
作者：
Jiang, Hui;Wang, Yue-Yue;Li, Yong-Quan
聚酮酶（PKS）的酰基转移酶（AT）结构域通常使用辅酶A（CoA）作为酰基供体将共同的酰基单元转移到酰基载体蛋白（ACP）结构域，启动酰基单元并入聚酮。两种临床免疫抑制剂FK506和FK520由几种链霉菌菌株中的相同PKS生物合成。在本研究中，在转酰反应中对AT 4（FkbB）（FK 506 PKS第四模块的AT结构域）进行了表征，结果表明AT 4（FkbB）识别ACP结构域（ACP（TcsA））和CoA作为酰基供体，将独特的烯丙基丙二酰（AM）单元转移至酰基受体ACP结构域（ACP 4（FkbB）），从而产生FK 506。此外，AT4（FkbB）使用CoA作为酰基供体将不寻常的乙基丙二酰（EM）单元转移到ACP 4（FkbB），导致FK520的产生，并将AM单元转移到非天然ACP受体。AT4（FkbB）在自酰化反应中的表征表明，AT4（FkbB）控制转酰化反应中的酰基单元特异性，但不控制自酰化反应中的酰基单元特异性。一般来说，PKS的AT结构域只识别一个酰基供体，然而，我们在这里报道，AT4（FkbB）识别两个酰基供体，用于转移不同的酰基单元。
Acyltransferase (AT) domains of polyketide synthases (PKSs) usually use coenzymeA (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.DatabaseNucleotide sequence data have been submitted to the GenBank database under accession numbers and .