## 1 Introduction  
_Hypericum perforatum_ L. ([PERSON] John's word) is a perennial herbaceous plant native to Europe, Northern Africa, Northern America and Asia [1, 2]. It has been used in folk medicine as a soothing, antiphlogistic and urogenital agent, as well as in the treatment of traumas, burns, scabs and hemorrhoids since Greek and Roman times [3]. Today, it is mainly used for antidepressant agents [4, 5, 6], which largely depend on the naphthodianthrone compound Hyp [3, 7]. Currently, Hyp is mainly extracted from _H. perforatum_[8]. In order to improve the Hyp production, many approaches that have been investigated include dissecting the Hyp biosynthetic pathway [9, 10, 11], screening germplasm resources [12, 13, 14], evaluating harvest stages [8, 12, 15], finding out the optimization of environmental factors such as nutrients [16], drought stress [17], UV-B radiation [18, 19, 20], light [21] and temperature [22, 20, 22, 23]. Hyp biosynthesis is started from glucose to acetyl- and malonyl-coenzyme A (CoA) in the cells of green tissues and from acetyl- and malonyl-CoA to Hyp in the cells of dark glands (Figure 1). Briefly, in green tissue, photosynthesis firstly produces glucose, and pyruvic acid is produced through glycolysis. Acetyl-CoA can be formed through pyruvate dehydrogenase. Malonyl-CoA can be derived from acetyl-CoA by acetyl-CoA carboxylase. In addition, acetyl-CoA can also be recycled as the result of the fatty acid metabolism. In the dark gland, one molecule of acetyl-CoA and seven molecules of malonyl-CoA form an octa-\(\beta\)-ketoacyl chain by polykiteide synthase (PKS) or octaketide synthase (OKS); emodin anthrone was formed after several steps, including aldolic condensation, thioesterase (TER), decarboxylic and dehydration reactions. Emodin dianthrone can be generated through two pathways, including the oxidation of emodin bianthrone, which is formed by the free radical coupling of emodin anthrone, and the synthesis of emodin anthrone and emodin by the phenoloxidative coupling protein (POCP). Then, Hyp is subsequently yielded via the catalysis of the berberine bridge enzyme (BBE) [9; 10; 11; 22; 24; 25; 26]. Experimental evidence shows that a low temperature improves Hyp production. Specifically, [PERSON] et al. [27] reported that a \(-\)4 \({}^{\circ}\)C treatment improved the Hyp content on a dry weight (DW) basis. [PERSON] et al. [20] found that the Hyp content on a DW basis in a root suspension culture reached the highest amount at 4 \({}^{\circ}\)C than at 8, 16 and 25 \({}^{\circ}\)C. [PERSON] et al. [28] determined that the genes (phenolic oxidative coupling protein (_Hyp-1_), _PKS1_ and _PKS2_) involved in Hyp synthesis were differentially expressed at different temperatures. Our previous studies found that 15 \({}^{\circ}\)C could enhance aerial parts of a biomass and Hyp contents of dry weight (DW) on a per plant basis, as well as mRNA expressions of the _hyp-1_ and _PKS_ genes, compared to 22 \({}^{\circ}\)C [22]. For the molecular function of _hyp-1_ gene, [PERSON] et al. [29] found that a conversion of emodin to Hyp was solely catalyzed by the _hyp-1_ gene, while [PERSON] et al. [30] reported that the _hyp-1_ gene is not a limiting factor for Hyp biosynthesis in the genus _Hypericum_ or that additional factors are necessary for completion. To date, the mechanism of low temperature regulating plant growth and Hyp biosynthesis in _H. perforatum_ is still limited. With the aim of unraveling the genes involved  
Figure 1: Pathway of Hyp biosynthesis from glucose to acetyl- and malonyl-coenzyme A (CoA) in the cells of green tissues (green frame) and from acetyl- and malonyl-CoA to Hyp in the cells of dark glands (black frame). PKS, polykitetidine synthase; OKS, octaketide synthase; TER, thioesterase; POCP, phenoloxidative coupling protein and BBE, berberine bridge enzyme.