Institute of Microbiology, Eidgenössische Technische Hochschule Zürich, Zurich, Switzerland.
Centre of Marine Sciences, University of Algarve, Faro, Portugal.
Nat Chem Biol. 2019 Aug;15(8):813-821. doi: 10.1038/s41589-019-0313-7. Epub 2019 Jul 15.
Bacterial trans-acyltransferase polyketide synthases (trans-AT PKSs) are among the most complex known enzymes from secondary metabolism and are responsible for the biosynthesis of highly diverse bioactive polyketides. However, most of these metabolites remain uncharacterized, since trans-AT PKSs frequently occur in poorly studied microbes and feature a remarkable array of non-canonical biosynthetic components with poorly understood functions. As a consequence, genome-guided natural product identification has been challenging. To enable de novo structural predictions for trans-AT PKS-derived polyketides, we developed the trans-AT PKS polyketide predictor (TransATor). TransATor is a versatile bio- and chemoinformatics web application that suggests informative chemical structures for even highly aberrant trans-AT PKS biosynthetic gene clusters, thus permitting hypothesis-based, targeted biotechnological discovery and biosynthetic studies. We demonstrate the applicative scope in several examples, including the characterization of new variants of bioactive natural products as well as structurally new polyketides from unusual bacterial sources.
细菌转酰基转移聚酮合酶（trans-AT PKSs）是次级代谢产物中已知的最复杂的酶之一，负责生物合成高度多样化的生物活性聚酮。然而，由于 trans-AT PKSs 经常存在于研究较少的微生物中，并且具有一系列功能尚未完全了解的非典型生物合成成分，因此大多数这些代谢物仍然未被描述。因此，基于基因组的天然产物鉴定具有挑战性。为了能够对 trans-AT PKS 衍生的聚酮进行从头结构预测，我们开发了 trans-AT PKS 聚酮预测器（TransATor）。TransATor 是一种多功能的生物和化学信息学网络应用程序，它可以为即使是高度异常的 trans-AT PKS 生物合成基因簇提供有意义的化学结构，从而允许基于假设的、有针对性的生物技术发现和生物合成研究。我们通过几个示例展示了其应用范围，包括生物活性天然产物的新型变体的表征以及来自不寻常细菌来源的结构新颖的聚酮。
