Bioinformatic Analysis Reveals both Oversampled and Underexplored Biosynthetic Diversity in Nonribosomal Peptides

Bo Siyuan Jian, Shao Lun Chiou, Chun Chia Hsu, Josh Ho, Yu Wei Wu, John Chu

研究成果: 雜誌貢獻文章同行評審

3 引文 斯高帕斯(Scopus)

摘要

The traditional natural product discovery approach has accessed only a fraction of the chemical diversity in nature. The use of bioinformatic tools to interpret the instructions encoded in microbial biosynthetic genes has the potential to circumvent the existing methodological bottlenecks and greatly expand the scope of discovery. Structural prediction algorithms for nonribosomal peptides (NRPs), the largest family of microbial natural products, lie at the heart of this new approach. To understand the scope and limitation of the existing prediction algorithms, we evaluated their performances on NRP synthetase biosynthetic gene clusters. Our systematic analysis shows that the NRP biosynthetic landscape is uneven. Phenylglycine and its derivatives as a group of NRP building blocks (BBs), for example, have been oversampled, reflecting an extensive historical interest in the glycopeptide antibiotics family. In contrast, the benzoyl BB, including 2,3-dihydroxybenzoate (DHB), has been the most underexplored, hinting at the possibility of a reservoir of as yet unknown DHB containing NRPs with functional roles other than a siderophore. Our results also suggest that there is still vast unexplored biosynthetic diversity in nature, and the analysis presented herein shall help guide and strategize future natural product discovery campaigns. We also discuss possible ways bioinformaticians and biochemists could work together to improve the existing prediction algorithms.
原文英語
頁(從 - 到)476-483
頁數8
期刊ACS Chemical Biology
18
發行號3
DOIs
出版狀態已發佈 - 2月 2023

ASJC Scopus subject areas

  • 生物化學
  • 分子醫學

指紋

深入研究「Bioinformatic Analysis Reveals both Oversampled and Underexplored Biosynthetic Diversity in Nonribosomal Peptides」主題。共同形成了獨特的指紋。

引用此