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Title: Synthetic biology based construction of biological activity-related library of fungal decalin-containing diterpenoid pyrones
Authors: Tsukada, Kento
Shinki, Shono
Kaneko, Akiho
Murakami, Kazuma  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0003-3152-1784 (unconfirmed)
Irie, Kazuhiro  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0001-7109-8568 (unconfirmed)
Murai, Masatoshi  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0001-6601-2854 (unconfirmed)
Miyoshi, Hideto
Dan, Shingo
Kawaji, Kumi
Hayashi, Hironori
Kodama, Eiichi N.
Hori, Aki
Salim, Emil
Kuraishi, Takayuki
Hirata, Naoya
Kanda, Yasunari
Asai, Teigo
Author's alias: 塚田, 健人
新木, 翔之
金子, 秋穂
村上, 一馬
入江, 一浩
村井, 正俊
三芳, 秀人
旦, 慎吾
河治, 久実
林, 宏典
児玉, 栄一
堀, 亜紀
倉石, 貴透
平田, 尚也
諫田, 泰成
浅井, 禎吾
Keywords: Combinatorial libraries
Genetic engineering
Metabolic engineering
Natural product synthesis
Issue Date: 14-Apr-2020
Publisher: Springer Nature
Journal title: Nature Communications
Volume: 11
Thesis number: 1830
Abstract: A synthetic biology method based on heterologous biosynthesis coupled with genome mining is a promising approach for increasing the opportunities to rationally access natural product with novel structures and biological activities through total biosynthesis and combinatorial biosynthesis. Here, we demonstrate the advantage of the synthetic biology method to explore biological activity-related chemical space through the comprehensive heterologous biosynthesis of fungal decalin-containing diterpenoid pyrones (DDPs). Genome mining reveals putative DDP biosynthetic gene clusters distributed in five fungal genera. In addition, we design extended DDP pathways by combinatorial biosynthesis. In total, ten DDP pathways, including five native pathways, four extended pathways and one shunt pathway, are heterologously reconstituted in a genetically tractable heterologous host, Aspergillus oryzae, resulting in the production of 22 DDPs, including 15 new analogues. We also demonstrate the advantage of expanding the diversity of DDPs to probe various bioactive molecules through a wide range of biological evaluations.
Rights: © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
URI: http://hdl.handle.net/2433/250909
DOI(Published Version): 10.1038/s41467-020-15664-4
PubMed ID: 32286350
Appears in Collections:Journal Articles

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