Department of Chemistry, University of Nebraska, Lincoln, Nebraska 68588, United States.
Biochemistry. 2012 Jan 10;51(1):4-6. doi: 10.1021/bi2015025. Epub 2011 Dec 23.
HSAF is an antifungal natural product with a new mode of action. A rare bacterial iterative PKS-NRPS assembles the HSAF skeleton. The biochemical characterization of the NRPS revealed that the thioesterase (TE) domain possesses the activities of both a protease and a peptide ligase. Active site mutagenesis, circular dichroism spectra, and homology modeling of the TE structure suggested that the TE may possess uncommon features that may lead to the unusual activities. The iterative PKS-NRPS is found in all polycyclic tetramate macrolactam gene clusters, and the unusual activities of the TE may be common to this type of hybrid PKS-NRPS.
HSAF 是一种具有新型作用模式的抗真菌天然产物。一种罕见的细菌迭代 PKS-NRPS 组装了 HSAF 骨架。NRPS 的生化特性表明硫酯酶（TE）结构域具有蛋白酶和肽连接酶的活性。TE 的活性位点突变、圆二色光谱和同源建模表明，TE 可能具有不常见的特征，从而导致其不寻常的活性。该迭代 PKS-NRPS 存在于所有多环四肽大环内酯基因簇中，而 TE 的不寻常活性可能在这种类型的混合 PKS-NRPS 中很常见。
