# Effect of PAS-LuxR Family Regulators on the Secondary Metabolism of _Streptomyces_
## 2 PAS-LuxR Family Regulators
### Structure of PAS-LuxR Family Regulators  
PAS-LuxR family regulators are a class of proteins containing a PAS-sensing structural domain at the N-terminal and a DBD region at the C-terminal with HTH [17]. PAS monitors light and oxygen changes in redox potential, and cellular energy and is a component of histidine and serine/threonine kinases, chemoreceptors, and photoreceptors that are involved in tropism, biological clock, and ion channels [8]. Unlike other sensing elements, proteins containing the PAS region are located in the cytosol and can directly sense signals inside the cell, while the above proteins can cross the cell membrane to sense signals from the external environment. The DBD region at the C-terminus of the PAS-LuxR family regulators is similar to that of LAL family regulators and is also derived from HTH-LuxR. The PAS-LuxR family regulators are highly conserved and generally consist of 152-243 amino acids, as shown in Figure 3. In its primary structure, the conserved region of PAS region is generally present in 1-130 amino acids, and the conserved amino acid residues are AX LDXXLITXXANAN\({}_{\text{n}}\)DXCGRXFXDXHPSVXQPLXRQFXXLXE. All the HTH structural domains are generally located at 117-221 amino acids, and their conserved amino acid residues are LX\({}_{\text{3}}\)DARILEGIAAGXSTYPLAAXLYLSRQGVEYHYTXLLRKLXVPNRAAL. In the secondary structure shown in Figure 4, all PAS domains contain the PAS core, helical  
Figure 2: Biosynthetic gene clusters containing the PAS-LuxR genes. Gln is a biosynthetic gene cluster that produces pimaricin in _S. childusoporeus_. Scn is a biosynthetic gene cluster that produces pimaricin in _S. childusoporeus_. Pim is a biosynthetic gene cluster that produces pimaricin from _S. childusoporeus_. Ttm is a biosynthetic gene cluster that produces tetramycin from _S. childusoporeus_. Txt is a biosynthetic gene cluster that produces tetramycin from _S. hysysys is a biosynthetic gene cluster for the production of nystain by _S. noursei_, Amph is a biosynthetic gene cluster that produces amphoteric from _S. nodosus_. Fsc is a biosynthetic gene cluster for the production of candididin by \(S\). sp. FR-008. Pte (Fil) is a biosynthetic gene cluster producing filipin from _S. avermitilis_ (_S. filipinensis_). Cfa is a biosynthetic gene cluster for the production of CFA-L-Ile by _S. schibi_. Rdm is a biosynthetic gene cluster that produces redsmycins from \(S\). sp. CHQ-64. NPP is a biosynthetic gene cluster that produces NPPA1 from _P. autotrophica_. Mar is a biosynthetic gene cluster that produces PF from _S. marokonensis_ M10. Sal is a biosynthetic gene cluster that produces salmonium from _S. albus_. The symbol of \(\Delta\) and \(|\) represent PAS-LuxR regulators coding genes and binding sites.  
connector, and \(\beta\)-scaffold. PAS core has the highest density of conserved residues in the PAS domain and is the key core region of PAS structure. The helical connector and \(\beta\)-scaffold are less conserved than the PAS core is [18]. The \(\beta\)-scaffold forms a long platform with a characteristic \(\beta\)-sheet that supports the PAS core. As illustrated in Figure 5, each regulator contains at least one HTH structure.  
Figure 4: Simulated secondary structures of N-terminal PAS structure of PAS-LuxR family regulators by SWISS-MODEL on [[https://swissmodel.expasy.org/](https://swissmodel.expasy.org/)]([https://swissmodel.expasy.org/](https://swissmodel.expasy.org/)), accessed on 25 July 2022.  
Figure 3: Sequence comparison of PAS-LuxR family regulatory factors. (**a**) PAS domain; (**b**) LuxR family HTH motif. X is an undefined amino acid residue.