Predicting the chemical space generated by fungal polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) hybrid

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K19214
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Agricultural chemistry and related fields
• Research Institution: Hokkaido University
• Principal Investigator: Minami Atsushi 北海道大学, 理学研究院, 准教授 (40507191)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Keywords: 天然物 / 生合成 / 酵素 / 構造予測

Outline of Final Research Achievements

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 important in the field of natural product chemistry. Here, we conducted a phylogenetic analysis of PKS–NRPSs 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 and 11 uncharacterized BGC groups. The limited number of carbon skeletons suggested that fungi tend to select PK skeletons for their survival during their evolution. This study provides insight into the chemical spaces of fungal PKs and the distribution of these biosynthetic gene clusters.

Free Research Field

天然物化学

Academic Significance and Societal Importance of the Research Achievements

多くの天然物化学者が「生物がどの程度の種類・数の天然物をつくることができるのか？」という点には興味を抱いているが、申請者の知る限りにおいて、明確な答えは得られていなかった。こうした状況下、申請者はバイオインフォマティクス解析の結果を化学的に解釈するという独自の方法論を提唱し、この問題を解決する端緒となる研究成果を得た。同様の手法により、他天然物の解析が進めば、上述した「問い」に対する回答が得られると期待される。