Exploring the Limits of Cyanobactin Macrocyclase PatGmac: Cyclization of PawS-Derived Peptide Sunflower Trypsin Inhibitor-1 and Cyclotide Kalata B1.
Exploring the Limits of Cyanobactin Macrocyclase PatGmac: Cyclization of PawS-Derived Peptide Sunflower Trypsin Inhibitor-1 and Cyclotide Kalata B1.
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DOI：
10.1021/acs.jnatprod.2c01158
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发表时间：
2023-03-24
影响因子：
5.1
通讯作者：
Goransson, Ulf
中科院分区：
文献类型：
--
作者：
Muhammad, Taj;Houssen, Wael E.;Thomas, Louise;Alexandru-Crivac, Cristina-Nicoleta;Gunasekera, Sunithi;Jaspars, Marcel;Goransson, Ulf
类枯草杆菌大环酶PatGmac是由海洋蓝藻普氯隆产生的。这种酶参与了生物合成的最后一步，即一种氰基结合蛋白类型的核糖体表达和翻译后修饰的环肽。PatGmac识别、切割和环化前体多肽之后，特定的识别基序组成的C-末端的尾巴与序列基序-AYDG。结果得到了天然的大环苯甲酰胺，它有八个氨基酸残基。可以通过将该基序结合到其他短线状肽前体中来利用大环酶活性，然后将其形成头尾相接的环化肽。在这里，我们探索了PatGmac用于大于Patellamide的多肽的环化的可能性，即爪子衍生的多肽向日葵胰蛋白酶抑制物-1(SFTI-1)和环肽Kalata B1。这些多肽属于两个不同的二硫化物限制的大环植物多肽家族。由于它们的结构和不同寻常的稳定性，它们都被认为是药物设计的支架。我们发现PatGmac可以有效地环化14个氨基酸残基Long SFTI-1，但不能有效环化29个氨基酸残基Long Kalata B1。
The subtilisin-like macrocyclase PatGmac is produced by the marine cyanobacterium Prochloron didemni. This enzyme is involved in the last step of the biosynthesis of patellamides, a cyanobactin type of ribosomally expressed and post-translationally modified cyclic peptides. PatGmac recognizes, cleaves, and cyclizes precursor peptides after a specific recognition motif comprised of a C-terminal tail with the sequence motif -AYDG. The result is the native macrocyclic patellamide, which has eight amino acid residues. Macrocyclase activity can be exploited by incorporating that motif in other short linear peptide precursors, which then are formed into head-to-tail cyclized peptides. Here, we explore the possibility of using PatGmac in the cyclization of peptides larger than the patellamides, namely, the PawS-derived peptide sunflower trypsin inhibitor-1 (SFTI-1) and the cyclotide kalata B1. These peptides fall under two distinct families of disulfide constrained macrocyclic plant peptides. They are both implicated as scaffolds for drug design due to their structures and unusual stability. We show that PatGmac can be used to efficiently cyclize the 14 amino acid residue long SFTI-1, but less so the 29 amino acid residue long kalata B1.
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影响因子：
16.8
作者：
Koehnke, Jesko;Bent, Andrew;Houssen, Wael E.;Zollman, David;Morawitz, Falk;Shirran, Sally;Vendome, Jeremie;Nneoyiegbe, Ada F.;Trembleau, Laurent;Botting, Catherine H.;Smith, Margaret C. M.;Jaspars, Marcel;Naismith, James H.
通讯作者：
Naismith, James H.
DOI：
10.3390/molecules27196430
发表时间：
2022-09-29
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Jacob B;Vogelaar A;Cadenas E;Camarero JA
通讯作者：
Camarero JA
影响因子：
--
作者：
Agarwal, Vinayak;Pierce, Elizabeth;Nair, Satish K.
通讯作者：
Nair, Satish K.
影响因子：
3.5
作者：
Craik, David J.;Lee, Meng-Han;Peacock, Hayden
通讯作者：
Peacock, Hayden
影响因子：
56.9
作者：
DAWSON, PE;MUIR, TW;KENT, SBH
通讯作者：
KENT, SBH