Laboratoire ProBioGEM, Université Lille1- Sciences et Technologies, Villeneuve d'Ascq, France.
LIFL, UMR CNRS 8022 Université Lille1 and INRIA Lille Nord Europe, Villeneuve d'Ascq, France.
PLoS One. 2014 Jan 21;9(1):e85667. doi: 10.1371/journal.pone.0085667. eCollection 2014.
Nonribosomal peptides represent a large variety of natural active compounds produced by microorganisms. Due to their specific biosynthesis pathway through large assembly lines called NonRibosomal Peptide Synthetases (NRPSs), they often display complex structures with cycles and branches. Moreover they often contain non proteogenic or modified monomers, such as the D-monomers produced by epimerization. We investigate here some sequence specificities of the condensation (C) and epimerization (E) domains of NRPS that can be used to predict the possible isomeric state (D or L) of each monomer in a putative peptide. We show that C- and E- domains can be divided into 2 sub-regions called Up-Seq and Down-Seq. The Up-Seq region corresponds to an InterPro domain (IPR001242) and is shared by C- and E-domains. The Down-Seq region is specific to the enzymatic activity of the domain. Amino-acid signatures (represented as sequence logos) previously described for complete C-and E-domains have been restricted to the Down-Seq region and amplified thanks to additional sequences. Moreover a new Down-Seq signature has been found for Ct-domains found in fungi and responsible for terminal cyclization of the peptides. The identification of these signatures has been included in a workflow named Florine, aimed to predict nonribosomal peptides from NRPS sequence analyses. In some cases, the prediction of isomery is guided by genus-specific rules. Florine was used on a Pseudomonas genome to allow the determination of the type of pyoverdin produced, the update of syringafactin structure and the identification of novel putative products.
非核糖体肽是由微生物产生的具有多种生物活性的天然化合物。由于它们通过称为非核糖体肽合成酶（NRPSs）的大型装配线进行特定的生物合成途径，因此它们通常具有带有环和分支的复杂结构。此外，它们通常包含非蛋白或修饰的单体，例如通过差向异构化产生的 D-单体。我们在这里研究了 NRPS 的缩合（C）和差向异构化（E）结构域的一些序列特异性，这些特异性可用于预测假定肽中每个单体的可能异构状态（D 或 L）。我们表明，C 和 E 结构域可以分为两个称为 Up-Seq 和 Down-Seq 的子区域。Up-Seq 区域对应于 InterPro 结构域（IPR001242），并且与 C 和 E 结构域共享。Down-Seq 区域是该结构域酶活性的特异性。先前针对完整 C 和 E 结构域描述的氨基酸特征（表示为序列徽标）已被限制在 Down-Seq 区域内，并通过附加序列进行了放大。此外，还发现了一种新的 Down-Seq 特征，用于真菌中的 Ct 结构域，该结构域负责肽的末端环化。这些特征的鉴定已包含在一个名为 Florine 的工作流程中，该流程旨在通过 NRPS 序列分析预测非核糖体肽。在某些情况下，异构性的预测受属特异性规则的指导。Florine 被用于假单胞菌基因组，以确定产生的绿脓菌素类型，更新 syringafactin 结构并鉴定新的潜在产物。
