Advances in Research on Swainsonine Biosynthesis Pathway and Related Genes in Fungi

doi:10.13523/j.cb.2303051

China Biotechnology

2023, Vol. 43

Issue (10): 109-119 DOI: 10.13523/j.cb.2303051

Advances in Research on Swainsonine Biosynthesis Pathway and Related Genes in Fungi

YANG Fan,LU Ping^**(

)

College of Life Science and Technology, Inner Mongolia Normal University, Hohhot 010022, China

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Abstract

The indolizidine alkaloid swinsonine (SW), which is produced by fungi, induces severe locoweed diseases in mammals. SW is a potential anti-cancer medication. Different fungi have various swainsonine synthesis pathways. A number of genes regulate the secondary metabolism of SW synthesis pathways. Early research revealed that the sac gene can promote the level of SW produced. Subsequently, P5CR (pyrroline-5-carboxylate reductase), a catalytic enzyme for the synthesis of pipecolic acid, has been found in endophytic fungi of locoweed. Later, the SWN gene cluster is proposed and the enzymes that each gene in the SWN gene cluster encodes for are mainly responsible for catalyzing the reactions that transform pipecolic acid to SW. In this paper, the research on the SW synthetic pathways of Rhizoctonia leguminicola, Metarhizium robertsii, and endophytic fungi of locoweed is reviewed.

Key words： Endophytic fungi Swainsonine Secondary metabolism SWN gene cluster

Received: 20 March 2023 Published: 02 November 2023

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YANG Fan, LU Ping. Advances in Research on Swainsonine Biosynthesis Pathway and Related Genes in Fungi. China Biotechnology, 2023, 43(10): 109-119.

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https://manu60.magtech.com.cn/biotech/10.13523/j.cb.2303051 OR https://manu60.magtech.com.cn/biotech/Y2023/V43/I10/109

Fig.1 Structure of SW

Fig.2 Partial synthesis pathways of SW from Rhizoctonia leguminicola

Fig.3 Partial synthesis pathways of SW in Metarhizium robertsii^[11]

Fig.4 Synthesis pathways of SW in M. robertsii^[21] 1: P6C; 2: Pipecolic acid; 3: (8aS)-1-Oxoindolizidine; 4: (1S, 8aS)-1-Hydroxyindolizine; 5: (1R, 8aS)-1-Hydroxyindolizine; 6: (1R, 2S, 8aS)-1, 2-Dihydroxyindolizine; 7: (1S, 2S, 8aS)-1, 2-Dihydroxyindolizine; 8: (1S, 2R, 8aS)-1, 2-Dihydroxyindolizine

Fig.5 Prediction of SW biosynthetic pathway in Alternaria oxytropis OW7.8 LYS1: Saccharopine reductase[NAD(+), L-lysine-forming] [EC:1.5.1.7]; LYS9: Saccharopine reductase(NADP, L-glutamate-forming) [EC:1.5.1.10]; lysDH: L-Lysine-6-dehydrogenase [EC:1.4.1.18]; AASS: Alpha-aminoadipic semialdehyde synthase [EC:1.5.1.8]; dpkA/lhpD: Delta-1-piperideine-2-carboxylate reductase [1.5.1.21]; lhpI:1-Piperideine-2-carboxylate reductase [EC:1.5.1.1]; PIPOX: Sarcosine oxidase/L-Pipecolate oxidase [EC:1.5.3.1][EC:1.5.3.7]

Fig.6 A two-way reaction catalyzed by saccharopine reductase ^[27]

Fig.7 Sac catalyzes the formation of P6C from L-lysine in Metarhizium anisopliae^[13]

Table 1 Predicted functions of SWN gene coding products

Table 2 PKS-NRPS domain encoded by swnK and its functions^[7,22]

Fig.8 The pathway catalyzed by each domain of the protein encoded by the swnK gene

Fig.9 Synthesis pathways of pipecolic acid


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