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Predicting the chemical space of fungal polyketides by phylogeny-based bioinformatics analysis of polyketide synthase-nonribosomal peptide synthetase and its modification enzymes
Title: | Predicting the chemical space of fungal polyketides by phylogeny-based bioinformatics analysis of polyketide synthase-nonribosomal peptide synthetase and its modification enzymes |
Authors: | Minami, Atsushi Browse this author →KAKEN DB | Ugai, Takahiro Browse this author | Ozaki, Taro Browse this author | Oikawa, Hideaki Browse this author |
Issue Date: | 11-Aug-2020 |
Publisher: | Nature Publishing Group |
Journal Title: | Scientific reports |
Volume: | 10 |
Issue: | 1 |
Start Page: | 13556 |
Publisher DOI: | 10.1038/s41598-020-70177-w |
Abstract: | Fungal polyketide synthase (PKS)-nonribosomal peptide synthetase (NRPS) hybrids are key enzymes for synthesizing structurally diverse hybrid natural products (NPs) with characteristic biological activities. Predicting their chemical space is of particular importance in the field of natural product chemistry. However, the unexplored programming rule of the PKS module has prevented prediction of its chemical structure based on amino acid sequences. Here, we conducted a phylogenetic analysis of 884 PKS-NRPS hybrids and a modification enzyme analysis of the corresponding biosynthetic gene cluster, revealing a hidden relationship between its genealogy and core structures. This unexpected result allowed us to predict 18 biosynthetic gene cluster (BGC) groups producing known carbon skeletons (number of BGCs; 489) and 11 uncharacterized BGC groups (171). The limited number of carbon skeletons suggests that fungi tend to select PK skeletons for survival during their evolution. The possible involvement of a horizontal gene transfer event leading to the diverse distribution of PKS-NRPS genes among fungal species is also proposed. This study provides insight into the chemical space of fungal PKs and the distribution of their biosynthetic gene clusters. |
Type: | article |
URI: | http://hdl.handle.net/2115/79505 |
Appears in Collections: | 理学院・理学研究院 (Graduate School of Science / Faculty of Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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