Muchiri Ruth, Walker Kevin D
Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA.
Chem Biol. 2012 Jun 22;19(6):679-85. doi: 10.1016/j.chembiol.2012.05.007.
In Taxus plants the biosynthesis of the pharmaceutical paclitaxel includes the transfer of β-amino phenylpropanoyls from coenzyme A to the diterpenoid baccatin III by an acyl CoA-dependent acyltransferase. Several enzymes on the pathway are known, yet a few remain unidentified, including the putative ligase that biosynthesizes key β-amino phenylpropanoyl CoAs. The multienzyme, nonribosomal peptide synthetase that produces tyrocidines contains a tridomain starter module tyrocidine synthetase A that normally activates (S)-α-Phe to an adenylate anhydride in the adenylation domain. The Phe moiety is then thioesterified by the pendent pantetheine of the adjacent thiolation domain. Herein, the adenylation domain was found to function as a CoA ligase, making α-, β-phenylalanyl, and phenylisoserinyl CoA. The latter two are substrates of a phenylpropanoyltransferase on the biosynthetic pathway of the antimitotic paclitaxel.
在红豆杉属植物中，药用紫杉醇的生物合成包括β-氨基苯丙酰基通过酰基辅酶A依赖性酰基转移酶从辅酶A转移至二萜类化合物浆果赤霉素III。该途径中的几种酶已为人所知，但仍有一些未被鉴定，包括推测的负责生物合成关键β-氨基苯丙酰辅酶A的连接酶。产生短杆菌酪肽的多酶非核糖体肽合成酶包含一个三结构域起始模块短杆菌酪肽合成酶A，该模块通常在腺苷化结构域中将（S）-α-苯丙氨酸激活为腺苷酸酐。然后，苯丙氨酸部分通过相邻硫醇化结构域的侧链泛酰巯基乙胺进行硫酯化。在此，发现腺苷化结构域可作为辅酶A连接酶，生成α-、β-苯丙氨酰和苯基异丝氨酰辅酶A。后两者是抗有丝分裂紫杉醇生物合成途径中苯丙酰转移酶的底物。
