Department of Biological and Irrigation Engineering, Utah State University, 4105 Old Main Hill, Logan, UT 84322-4105, USA.
Curr Top Med Chem. 2009;9(17):1958-610. doi: 10.2174/156802609789941906.
Aromatic polyketides represent important members of the family of polyketides, which have displayed a wide assortment of bioactive properties, such as antibacterial, antitumor, and antiviral activities. Bacterial aromatic polyketides are mainly synthesized by type II polyketide synthases (PKSs). Whereas malonyl-CoA is exclusively used as the extender unit, starter units can vary in different aromatic polyketide biosynthetic pathways, leading to a variety of polyketide backbones. Once the polyketide chains are elongated by the minimal PKSs to the full length, the immediate tailoring enzymes including ketoreductases, oxygenases and cyclases will work on the nascent chains to form aromatic structures, which will be further decorated by those late tailoring enzymes such as methyltransferases and glycosyltransferases. The mechanistic studies on the biosynthetic pathways of aromatic polyketides such as oxytetracycline and pradimicin A have been extensively carried out in recent years. Engineered biosynthesis of novel "unnatural" polyketides has been achieved in heterologous hosts such as Streptomyces coelicolor and Escherichia coli. This review covers the most recent advances in aromatic polyketide biosynthesis, which provide new enzymes or methods for building novel polyketide biosynthetic machinery.
芳香族聚酮化合物是聚酮化合物家族的重要成员，具有广泛的生物活性，如抗菌、抗肿瘤和抗病毒活性。细菌芳香族聚酮化合物主要由 II 型聚酮合酶（PKSs）合成。虽然丙二酰辅酶 A 是唯一的延伸单元，但起始单元在不同的芳香族聚酮生物合成途径中可能不同，从而导致各种聚酮骨架的形成。一旦最小的 PKS 将聚酮链延长到全长，立即的修饰酶，包括酮还原酶、加氧酶和环化酶，将作用于新生链上，形成芳香结构，这些结构将进一步由那些晚期修饰酶如甲基转移酶和糖基转移酶进行修饰。近年来，对土霉素和普拉霉素 A 等芳香族聚酮生物合成途径的机制研究已经广泛开展。在链霉菌和大肠杆菌等异源宿主中实现了新型“非天然”聚酮的工程化生物合成。本综述涵盖了芳香族聚酮生物合成的最新进展，为构建新型聚酮生物合成机制提供了新的酶或方法。
