Unveiling of Swainsonine Biosynthesis via a Multibranched Pathway in Fungi

doi:10.1021/acschembio.0c00466

	Unveiling of Swainsonine Biosynthesis via a Multibranched Pathway in Fungi
	Luo, Feifei 1,2; Hong, Song 2; Chen, Bo 2; Yin, Ying 2; Tang, Guirong 2; Hu, Fenglin 3; Zhang, Huizhan 1; Wang, Chengshu2,4
	2020-09-18
发表期刊	ACS CHEMICAL BIOLOGY (IF:3.5[JCR-2023],3.9[5-Year])
ISSN	1554-8929
卷号	15 期号:9 页码:2476-2484
DOI	10.1021/acschembio.0c00466
摘要	The indolizidine alkaloid swainsonine (SW) is a deadly mycotoxin to livestock that can be produced by different plant-associated fungi, including the endophytic entomopathogenic fungi Metarhizium species. The SW biosynthetic gene cluster has been identified but the genetic mechanism of SW biosynthesis remains obscure. To unveil the SW biosynthetic pathway, we performed gene deletions in M. robertsii, heterologous expression of a core biosynthetic gene, substrate feedings, mass spectrometry, and bioassay analyses in this study. It was unveiled that SW is produced via a multibranched pathway by the hybrid non-ribosomal peptide-polyketide synthase (NRPS-PKS) gene cluster in M. robertsii. The precursor pipecolic acid can be converted from lysine by both the SW biosynthetic cluster and the unclustered genes such as lysine cyclodeaminase. The hybrid NRPS-PKS enzyme produces three intermediates with and without domain skipping. Intriguingly, the biosynthetic process is coupled with the cis to trans nonenzymatic epimerization of C1-OH for both hydroxyl- and dihydroxyl-indolizidine intermediates. We also found that SW production was dispensable for fungal colonization of plants and infection of insect hosts. Functional characterization of the SW biosynthetic genes in this study may benefit the safe use of Metarhizium fungi as insect biocontrol agents and the management of livestock pastures from SW contamination by genetic manipulation of the toxin -producing fungi.
收录类别	SCI ; SCIE
语种	英语
资助项目	National Natural Science Foundation of China[31530001] ; Shanghai Academic/Technology Researcher Leader Program[18XD1404500]
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
WOS记录号	WOS:000574920900016
出版者	AMER CHEMICAL SOC
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/123551
专题	生命科学与技术学院_特聘教授组_王成树组
通讯作者	Wang, Chengshu
作者单位	1.East China Univ Sci & Technol, Sch Biotechnol, Shanghai 200237, Peoples R China; 2.Chinese Acad Sci, CAS Ctr Excellence Mol Plant Sci, Shanghai Inst Plant Physiol & Ecol, CAS Key Lab Insect Dev & Evolutionary Biol, Shanghai 200032, Peoples R China; 3.Anhui Agr Univ, Anhui Prov Key Lab Microbial Pest Control, Hefei 230061, Peoples R China; 4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Luo, Feifei,Hong, Song,Chen, Bo,et al. Unveiling of Swainsonine Biosynthesis via a Multibranched Pathway in Fungi[J]. ACS CHEMICAL BIOLOGY,2020,15(9):2476-2484.
APA	Luo, Feifei.,Hong, Song.,Chen, Bo.,Yin, Ying.,Tang, Guirong.,...&Wang, Chengshu.(2020).Unveiling of Swainsonine Biosynthesis via a Multibranched Pathway in Fungi.ACS CHEMICAL BIOLOGY,15(9),2476-2484.
MLA	Luo, Feifei,et al."Unveiling of Swainsonine Biosynthesis via a Multibranched Pathway in Fungi".ACS CHEMICAL BIOLOGY 15.9(2020):2476-2484.