Department of Chemistry, University of Tennessee-Knoxville, Knoxville, TN 37996, USA.
Department of Chemistry, University of Tennessee-Knoxville, Knoxville, TN 37996, USA; School of Chemistry, The University of Sydney, Camperdown, New South Wales 2006, Australia.
Bioorg Med Chem Lett. 2023 Jul 15;91:129377. doi: 10.1016/j.bmcl.2023.129377. Epub 2023 Jun 14.
In primary metabolism, fatty acid synthases (FASs) biosynthesize fatty acids via sequential Claisen-like condensations of malonyl-CoA followed by reductive processing. Likewise, polyketide synthases (PKSs) share biosynthetic logic with FAS which includes utilizing the same precursors and cofactors. However, PKS biosynthesize structurally diverse, complex secondary metabolites, many of which are pharmaceutically relevant. This digest covers examples of interconnected biosynthesis between primary and secondary metabolism in fatty acid and polyketide metabolism. Taken together, further understanding the biosynthetic linkage between polyketide biosynthesis and fatty acid biosynthesis may lead to improved discovery and production of novel drug leads from polyketide metabolites.
在初级代谢中，脂肪酸合酶（FAS）通过丙二酰辅酶 A 的连续 Claisen 样缩合，然后进行还原处理来合成脂肪酸。同样，聚酮合酶（PKS）与 FAS 具有相似的生物合成逻辑，包括利用相同的前体和辅因子。然而，PKS 合成结构多样、复杂的次级代谢产物，其中许多与药物有关。这篇综述涵盖了脂肪酸和聚酮代谢中初级代谢和次级代谢之间相互关联的生物合成的例子。总的来说，进一步了解聚酮生物合成和脂肪酸生物合成之间的生物合成联系，可能会导致从聚酮代谢物中发现和生产新型药物先导物的能力得到提高。
