L-proline (L-Pro) is the only imino acid among the 20 amino acids that constitute biological proteins, and its main hydroxylated product is trans-4-hydroxy-L-proline (T-4-Hyp). Both of them have unique biological activities and play important roles in biomedicine, food and beauty industry. With the in-depth exploration of the functions of L-Pro and T-4-Hyp, the demand for them is gradually increasing. Traditional methods of biological extraction and chemical synthesis are unable to meet the demand of "green, environmental protection and high efficiency". In recent years, synthetic biology has developed rapidly. Through the intensive analysis of the synthetic pathways of L-Pro and T-4-Hyp, microbial cell factories were constructed for large-scale production, which opened a new chapter for the green and efficient production of L-Pro and T-4-Hyp. This paper reviews the application and production methods of L-Pro and T-4-Hyp, the metabolic pathways for microbial synthesis of L-Pro and T-4-Hyp, and the engineering strategies and advances on microbial production of L-Pro and T-4-Hyp, aiming to provide a theoretical basis for the "green bio-manufacturing" of L-Pro and T-4-Hyp and promote their industrial production.
Proline ; Hydroxyproline

Ganoderma resinaceum tolerated sodium chloride salt stress within a range of 0 mM till 300 mM. It responded to salt stress with fluctuation in proline formation at different NaCl concentrations. However,the mycelial dry weight,total protein contents and exopolysaccharides did not changed considerably. Increasing sodium chloride concentration led to morphological alteration in fungal mycelia with disappearance of fungal cell wall,plasmolysis,and vacuolation as indicated with electron microscopic examination of the fungal growth.
Ganoderma* ; Proline ; Sodium Chloride* ; Sodium*

No abstract available in English.
Arthritis, Rheumatoid ; Dupuytren Contracture ; Osteoarthritis ; Proline

STATEMENT OF PROBLEM: In cases where bony defects were present, guided bone regenerations have been performed to aid the placement of implants. Nowadays, the accepted concept is to isolate bone from soft tissue by using barrier membranes to allow room for generation of new bone. Nonresorbable membranes have been used extensively since the 1980's. However, this material has exhibited major shortcomings. To overcome these faults, efforts were made to develop resorbable membranes. Guided bone regenerations utilizing resorbable membranes were tried by a number of clinicians. Bio-Gide. is such a bioresorbable collagen that is easy to use and has shown fine clinical results. PURPOSE: The aim of this study was to evaluate the histological results of guided bone regenerations performed using resorbable collagen membrane(Bio-Gide.) with autogenous bone, bovine drived xenograft and combination of the two. Surface morphology and chemical composition was analyzed to understand the physical and chemical characteristics of bioresorbable collagen membrane and their effects on guided bone regeneration. MATERIAL AND METHODS: Bioresorbable collagen membrane (Bio-Gide.), Xenograft Bone(Bio-Oss), Two healthy, adult mongrel dogs were used. RESULTS: 1. Bioresorbable collagen membrane is pure collagen containing large amounts of Glysine, Alanine, Proline and Hydroxyproline. 2. Bioresorbable collagen membrane is a membrane with collagen fibers arranged more loosely and porously compared to the inner surface of canine mucosa : This allows for easier attachment by bone-forming cells. Blood can seep into these spaces between fibers and form clots that help stabilize the membrane. The result is improved healing. 3. Bioresorbable collagen membrane has a bilayered structure : The side to come in contact with soft tissue is smooth and compact. This prevents soft tissue penetration into bony defects. As the side in contact with bone is rough and porous, it serves as a stabilizing structure for bone regeneration by allowing attachment of bone-forming cells. 4. Regardless of whether a membrane had been used or not, the group with autogenous bone and Bio-Oss. filling showed the greatest amount of bone fill inside a hole, followed by the group with autogenous bone filling, the group with blood and the group with Bio-Oss. Filling in order. 5. When a membrane was inserted, regardless of the type of bone substitute used, a lesser amount of resorption occurred compared to when a membrane was not inserted. 6. The border between bone substitute and surrounding bone was the most indistinct with the group with autogenous bone filling, followed by the group with autogenous bone and Bio-Oss. filling, the group with blood, and the group with Bio-Oss. filling. 7. Three months after surgery, Bio-Gide. and Bio-Oss. were distinguishable. CONCLUSION: The best results were obtained with the group with autogenous bone and Bio-Oss. filling used in conjunction with a membrane.
Adult ; Alanine ; Animals ; Autografts* ; Bone Regeneration ; Bone Substitutes ; Collagen* ; Dogs ; Guided Tissue Regeneration ; Heterografts* ; Humans ; Hydroxyproline ; Membranes* ; Mucous Membrane ; Proline ; Regeneration*

OBJECTIVE: Many neurochemical systems have been implicated in the development of Posttraumatic Stress Disorder (PTSD). The prolidase enzyme is a cytosolic exopeptidase that detaches proline or hydroxyproline from the carboxyl terminal position of dipeptides. Prolidase has important biological effects, and to date, its role in the etiology of PTSD has not been studied. In the present study, we aimed to evaluate prolidase activity in patients with PTSD. METHODS: The study group consisted of patients who were diagnosed with PTSD after the earthquake that occurred in the province of Van in Turkey in 2011 (n=25); the first control group consisted of patients who experienced the earthquake but did not show PTSD symptoms (n=26) and the second control group consisted of patients who have never been exposed to a traumatic event (n=25). Prolidase activities in the patients and the control groups were determined by the ELISA method using commercial kits. RESULTS: Prolidase activity in the patient group was significantly lower when compared to the control groups. Prolidase activity was also significantly lower in the traumatized healthy subjects compared to the other healthy group (p<0.01). CONCLUSION: The findings of the present study suggest that the decrease in prolidase activity may have neuroprotective effects in patients with PTSD.
Cytosol ; Dipeptides ; Earthquakes ; Enzyme-Linked Immunosorbent Assay ; Exopeptidases ; Healthy Volunteers ; Humans ; Hydroxyproline ; Methods ; Neuroprotective Agents ; Proline ; Stress Disorders, Post-Traumatic* ; Turkey

OBJECTIVES: Although increased reactive oxygen species (ROS) is caused by stress accelerates collagen degradation, there was no data on the relationship between stress and urinary hydroxyproline (Hyp) and proline (Pro), a good marker of collagen degradation. The purpose of this study was to evaluate the relationship between depression, anxiety, and stress (DAS) and concentrations of urinary Hyp and Pro. METHODS: 97 hospital employees aged 20 to 58 were asked to fill out comprehensive self-administrated questionnaires containing information about their medical history, lifestyle, length of the work year, shit-work and DAS. Depression Anxiety Stress Scale (DASS) was applied to evaluate chronic mental disorders. Urine samples were analyzed using High Performance Liquid Chromatography (HPLC) with double derivatization for the assay of hydroxyproline and proline. RESULTS: The mean value of Hyp and Pro concenturation in all subjects was 194.1+/-113.4 micromol/g and 568.2+/-310.7 micromol/g. DASS values and urinary Pro concentrations were differentiated by sex (female > male, p < 0.05) and type of job (nurse > others, p < 0.05). In the stepwise multiple linear regressions, urinary Hyp and Pro concentrations were influenced by stress (Adjusted r2 = 0.051) and anxiety and job (Adjusted r2 = 0.199), respectively. CONCLUSIONS: We found that stress and anxiety were correlated with urinary Hyp and Pro concentrations. To identifying a definite correlation, further study in large populations will be needed.
Adult ; Anxiety/*urine ; Depression/*urine ; Female ; Humans ; Hydroxyproline/urine ; Male ; Middle Aged ; Personnel, Hospital/*psychology ; Proline/*urine ; Questionnaires ; Republic of Korea ; Stress, Psychological/*urine ; Young Adult

The effect of L-proline as a promoter on the condensation reaction of salicylaldehyde or its derivatives with ethyl acetoacetate in neutral ionic liquid [emim]BF4 was studied. All reactions were carried out under mild reaction conditions and achieved high yields. Moreover, the ionic liquid containing L-proline could be recycled and reused for several times without noticeably decreasing in productivity. The results show that the L-proline-[emim]BF4 system has a potential in contribution to the development of environmentally friendly and inexpensive processes in organic syntheses.
Coumarins ; chemical synthesis ; Ionic Liquids ; chemistry ; Proline ; chemistry

Glutamate decarboxylase, a unique pyridoxal 5'-phosphate-dependent enzyme, catalyzes α-decarboxylation of L-glutamate to γ-aminobutyrate. However, glutamate decarboxylase from different sources has the common problem of poor thermostability that affects its application in industry. In this study, proline was introduced at 13 different positions in glutamate decarboxylase by using the design strategy of homologous sequence alignment between Thermococcus kodakarensis and Lactobacillus brevis CGMCC No.1306. A mutant enzyme G364P with higher thermostability was obtained. Compared to the wild type, thermostability of the mutant G364P was significantly improved, the half-life time (t1/2) at 55 °C and the semi-inactivation temperature (T₅₀ ¹⁵) of the mutant G364P increased 19.4 min and 5.3 °C, respectively, while kcat/Km of the mutant enzyme remained nearly unchanged. Further analysis of their thermostability by molecular dynamics simulations were performed. The root mean square deviation of G364P and root mean square fluctuation in the loop region including G364 were lower than the wild type at 313 K for 10 ns, and G364P increased one hydrophobic interaction in the loop region. It proves that mutation of flexible 364-Gly to rigid proline endows glutamate decarboxylase with enhanced thermostability.
Glutamate Decarboxylase ; Glutamic Acid ; Lactobacillus brevis ; Molecular Dynamics Simulation ; Proline

Retinal pigment epithelial(RPE) cells play a important role in proliferative retinopathy(PVR) by the collagen production involved in the formation of PVR membrane. To evaluate the effect of L-azetidine-2-carvoxylic acid(LACA), a proline analogue, known as depressing the abnormal cell proliferation and PVR membrane formation, we examined the proliferation, collagen synthesis and migration of cultured bonine RPE cells following the addition of LACA. Differant concentrations of LACA as 1, 10, 50, 100microgram/ml was added to bovine RPE cells and cultured. The cell numbers were measured in 3, 6, 9 days, [3H]-thymidine uptake assay was done to evaluate the change of DNA synthesis, and collagen synthesis and cell migration was measured. The proliferation of PRE cells treated with LACA were significantly inhibited in a concentration and time dependant manner. [3H]-thymidine uptake and collagen synthesis of RPE migration was also significantly inhibited in proportion to the concentration. The results reveal that LACA has an inhibitory effect on cell proliferation, collagen synthesis and migration of bovine retinal pigment epithelial cells. It also suggest that the use of LACA to suppress membrane formation in the eyes with PVR can be possible.
Cell Count ; Cell Movement ; Cell Proliferation ; Collagen* ; DNA ; Epithelial Cells* ; Meclizine ; Membranes ; Proline ; Retinaldehyde* ; Vitreoretinopathy, Proliferative

The current standard of care for hepatitis C infection is peginterferon/ribavirin (PegIFN/RBV). We are entering the era where direct-acting antiviral agents (DAAs) will be added to PegIFN/RBV, leading to higher sustained response rates in genotype 1 infected individuals. Currently DAAs are directed toward specific proteins involved in hepatitis C replication with NS3/NS4A protease inhibitors furthest in development. Telaprevir and boceprevir are both NS3/NS4a inhibitors that significantly improve sustained response when added to PegIFN and RBV. The hepatitis C virus (HCV) polymerase inhibitors are another promising DAA class. These molecules are divided into nucleoside/nucleotide polymerase inhibitors and nonnucleotide/nucleoside polymerase inhibitors. Nucleoside/nucleotide polymerase inhibitors have a high barrier to resistance and appear to be effective across a broad range of genotypes. Nonnucleoside polymerase inhibitors have a lower barrier of resistance and appear to be genotype specific. Preliminary data with these compounds are also promising. A third class, NS5A inhibitors, has also shown potent HCV RNA suppression in preliminary studies as monotherapy and with PegIFN and RBV. Combinations of these agents are also entering clinical trials and indeed a preliminary report has demonstrated that the combination of an NS3/4A protease inhibitor and NS5B polymerase inhibitor can effectively suppress virus in genotype 1 individuals. Future studies will concentrate on combinations of direct-acting antiviral agents without and with PegIFN and RBV. Clinicians will need to be familiar with managing side effects as well as resistance as we enter this new era.
Antiviral Agents ; Genotype ; Hepacivirus ; Hepatitis ; Hepatitis C ; Oligopeptides ; Proline ; Protease Inhibitors ; Proteins ; RNA ; Standard of Care ; Viruses