Multi-objective optimization at a crude novel lipase catalyzed fame production: kriging as an alternative to rsm

Biyodizel özellikle transport sektörü açısından petrol kaynaklı dizel yakıtlara yenilenebilir ve potansiyel olarak sürdürülebilir bir alternatiftir. Biyodizel, ham, rafine veya atık yağlar ile hayvansal yağlar gibi çeşitli hammaddeler kullanılarak, katalitik olmayan ısıl yöntemler, homojen ya da heterojen kimyasal dönüşümler ve biyokatalitik dönüşümler ile üretilebilmektedir. Atık pişirme yağından elde edilen biyokatalitik biyodizel üretiminin ticari olarak uygulanabilirliği, hammaddedeki trigliseritlerin transesterifikasyonunu ve serbet yağ asitlerinin esterifikasyonunu katalizleyen lokal ve ekonomik olarak üretilme potansiyeli olan yeni lipazların mevcudiyetine bağlıdır. Bu açıdan, farklı kaynaklardan değişik özelliklere sahip farklı lipazların taranması, seçilmesi ve geliştirilmesi, lipaz katalizli biyodizel üretiminin cazip hale gelmesinde temel bir görevdir. Yeni lipazlar için erken değerlendirme deneyleri, değişen reaksiyon sıcaklığı, alkil reseptör substrat mol oranı ve enzim miktarı altında zamana bağlı değişimleri gözlemlemek için uygulanmaktadır. Bu erken dönem deneylerinden elde edilen ön veriler, yeni lipazların hızlı ve etkili bir şekilde değerlendirilmesini kolaylaştırmak için uygun modelleme ve optimizasyon şeması içinde kullanılmalıdır. Geleneksel olarak, düşük mertebeden polinom modellerine dayanan yanıt yüzey yöntemi, verim gibi tek hedefli optimizasyon için kullanılır. Bu çalışmada, Kriging ve Pareto-front çok hedefli optimizasyonunu kullanan alternatif bir modelleme ve optimizasyon yaklaşımı, geleneksel şemaya kıyasla her iki prosedürün uygulanabilirliği ve verimliliği ile ilgili konulara dikkat çekerek, yeni bir lipaza uygulanmaktadır. Kriging temelli modelleme ve optimizasyon yönteminin, sınırlı ön deneysel verilerin kullanılmasında avantajlı olduğu gösterilmiştir.--------------------Biodiesel is a renewable and potentially sustainable alternative to petroleum-based diesel, especially in the transportation sector. Biodiesel can be produced by non-catalytic thermal methods, homogenous or heterogenous chemical conversions, and biocatalytic transformations using various types of feedstock such as crude, refined or waste oils, or animal fats. Commercial feasibility of biocatalytic biodiesel production from waste cooking oil critically depends on the availability of novel lipases, which catalyze the transesterification of triglycerides and esterification of free fatty acids in the feedstock into fatty acid alkyl esters, with the potential to be locally and economically produced. In this respect, screening, selection, and development of different lipases with varying properties from different sources is an essential task towards making lipase-catalyzed biodiesel production an attractive endeavor. Early evaluation of novel lipases employs time progress experiments under varying reaction temperature, alkyl receptor to substrate molar ratio, and enzyme amount. The preliminary data acquired from these early experiments need to be used within an appropriate modelling and optimization scheme to facilitate rapid and efficient evaluation of the novel lipase. Conventionally, response surface methodology based on low-order polynomial models is used for the optimization of a single objective like yield. In this work, an alternative modelling and optimization approach employing Kriging and Pareto-front multi-objective optimization is applied to a novel lipase, in comparison to the conventional scheme, highlighting the issues regarding the applicability and efficiency of both procedures. Kriging-based modelling and optimization methodology is shown to be advantageous in making use of limited preliminary experimental data

Sikloartan grubu siklokantogenol ve astragenol saponinlerinin mikrobiyal biyotransformasyonu

Mikroorganizmalar tarafından çok çeşitli reaksiyonlar katalizlenmektedir. Mikrobiyal transformasyon, bazı biyolojik aktif ürünlerin yapılarının modifiye edilmesi ve doğal ürün metabolizmasının çalışılması açısından ekonomik ve ekolojik olarak uygulanabilir bir teknoloji olarak görülmektedir. Bu tezin amacı, farmakolojik etkilerinden dolayı son günlerde önemli hale gelmiş Astragalus cinsi sikloartan grubu sapogenollerinden olan siklokantogenol (SKG) ve astragenol (AG) üzerinde mikrobiyal transformasyon çalışmaları gerçekleştirmek, yeni türevler elde etmek ve sitotoksisitelerini incelemektir. Bu çalışmada, uygun besin ortamları kullanılarak Nocardia sp. NRRL 5646 bakterisi ile Cunninghamella blakesleeana ATCC 8688a (NRRL 1369) ve Glomerella fusarioides ATCC 9552 fungusları üretildikten sonra, organizmaların katalizlediği reaksiyonların sonucunda oluşan biyotransformasyon ürünleri incelenmiş ve karakterizasyonları yapılmıştır. Son olarak, oluşan yeni metabolitler, sitotoksisitelerinin belirlenmesi için MTT testine tabi tutulmuştur. C. blakesleeana fungusunun SKG ile gerçekleştirilen biyotransformasyon çalışması, C-11 pozisyonunda primer alkol içeren bir major molekülün eldesi ile sonuçlanırken, aynı fungusun AG ile yapılan biyotransformasyon çalışması sonucunda 3 farklı metabolit elde edilmiştir. Major molekülün C-12 pozisyonunda hidroksil grubu içerdiği belirlenmiştir. Diğer iki molekül 10,11 epoksi halkasına sahip olduğu bulunmuştur ve bunlardan birinin ayrıca C-6 pozisyonunda hidroksil grubu yerine keton grubu taşıdığı saptanmıştır. G. fusarioides fungusunun SKG ile yapılan biyotransformasyon çalışması sonucunda Baeyer-Villiger tipi oksidasyon sonrası 3,4-seko ürün oluşmuştur. Sonuç olarak beş biyotransformasyon ürünü elde edilmiştir ve bu bileşikler doğa ve literatür için yenidir. Ayrıca biyotransformasyon ürünleri kanser hücre hatlarına karşı anlamlı sitotoksisite göstermemiştir (>100 μg/mL)

Microbial transformation of Astragalus sapogenins using Cunninghamella blakesleeana NRRL 1369 and Glomerella fusarioides ATCC 9552

The microbial transformation of Astragalus sp. derived sapogenins, namely cycloastragenol, astragenol and cyclocanthogenol, by Cunninghamella blakesleeana NRRL 1369 and Glomerella fusarioides ATCC 9552 were investigated. The unique enzyme system of both fungi resulted hydroxylation, cyclization, dehydrogenation and oxidation reactions. Structures of the new metabolites were elucidated by 1-D (1H, 13C, NOESY), 2-D NMR (DQF-COSY, HMBC, HMQC, NOESY) and HR-MS analyses. © 2015 Elsevier B.V

Multi-objective optimization of a novel crude lipase-catalyzed fatty acid methyl ester (FAME) production using low-order polynomial and Kriging models

In this paper, conventional response surface methodology (RSM) based on low-order polynomials and an alternative Kriging-based method are used for the model-based single and multi-objective optimization of fatty-acid methyl ester (FAME) production catalyzed by a novel crude lipase from the yeast Cryptococcus diffluens (D44). The coefficient of determination for the two modeling approaches was calculated as 0.97 for the Kriging method, and 0.86 for RSM; showing a more reliable representation of experimental data by Kriging. Both models were used to perform single (maximizing FAME titer and temporal productivity separately) and multi-objective (maximizing FAME titer and temporal productivity simultaneously) optimizations of four important operating conditions (reaction time and temperature; amount of crude enzyme; and volume of methanol used). In all cases, the highest temperature considered (60 degrees C) gave the best results. A reduction of reaction time in half was seen to be necessary to achieve optimum productivity compared to titer, when the two objectives were considered separately. The observed trade-off between the two objectives was quantified via multi-objective optimization using Pareto-front analysis

Microbial transformation of Astragalus sapogenins using Cunninghamella blakesleeana NRRL 1369 and Glomerella fusarioides ATCC 9552

WOS: 000353599300005The microbial transformation of Astragalus sp. derived sapogenins, namely cycloastragenol, astragenol and cyclocanthogenol, by Cunninghamella blakesleeana NRRL 1369 and Glomerella fusarioides ATCC 9552 were investigated. The unique enzyme system of both fungi resulted hydroxylation, cyclization, dehydrogenation and oxidation reactions. Structures of the new metabolites were elucidated by 1-D (H-1, C-13, NOESY), 2-D NMR (DQF-COSY, HMBC, HMQC, NOESY) and HR-MS analyses. (C) 2015 Elsevier B.V. All rights reserved.Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [109S345]; European Cooperation in Science and Technology (COST, Action)European Cooperation in Science and Technology (COST) [CM0804]This work is supported by The Scientific and Technological Research Council of Turkey (TUBITAK, Project No: 109S345) and European Cooperation in Science and Technology (COST, Action No: CM0804). The fungi, Cunninghamella blakesleeana NRRL 1369 was obtained from the ARS Culture Collection, USA, and Glomerealla fusarioides ATCC 9552 was obtained from LGC Standards-ATCC Culture Collection. Finally, we are very greatful to Biological Mass Spectrometry and Proteomics Facility, Izmir Institute of Technology, Department of Chemistry for obtaining mass spectra

Attenuation of Type IV pili activity by natural products

The virulence factor Type IV pili (T4P) are surface appendages used by the opportunistic pathogen Pseudomonas aeruginosa for twitching motility and adhesion in the environment and during infection. Additionally, the use of these appendages by P. aeruginosa for biofilm formation increases its virulence and drug resistance. Therefore, attenuation of the activity of T4P would be desirable to control P. aeruginosa infections. Here, a computational approach has been pursued to screen natural products that can be used for this purpose. PilB, the elongation ATPase of the T4P machinery in P. aeruginosa, has been selected as the target subunit and virtual screening of FDA-approved drugs has been conducted. Screening identified two natural compounds, ergoloid and irinotecan, as potential candidates for inhibiting this T4P-associated ATPase in P. aeruginosa. These candidate compounds underwent further rigorous evaluation through molecular dynamics (MD) simulations and then through in vitro twitching motility and biofilm inhibition assays. Notably, ergoloid emerged as a particularly promising candidate for weakening the T4P activity by inhibiting the elongation ATPases associated with T4P. This repurposing study paves the way for the timely discovery of antivirulence drugs as an alternative to classical antibiotic treatments to help combat infections caused by P. aeruginosa and related pathogens. Communicated by Ramaswamy H. Sarma</p

Evaluation of abdominal computed tomography findings in patients with COVID-19: a multicenter study

PURPOSE To evaluate the frequency of abdominal computed tomography (CT) findings in patients with coronavirus disease-2019 (COVID-19) and interrogate the relationship between abdominal CT findings and patient demographic features, clinical findings, and laboratory test results as well as the CT atherosclerosis score in the abdominal aorta. METHODS This study was designed as a multicenter retrospective study. The abdominal CT findings of 1.181 patients with positive abdominal symptoms from 26 tertiary medical centers with a positive polymerase chain-reaction test for severe acute respiratory syndrome coronavirus 2 were reviewed. The frequency of ischemic and non-ischemic CT findings as well as the association between CT findings, clinical features, and abdominal aortic calcific atherosclerosis score (AA-CAS) were recorded. RESULTS Ischemic and non-ischemic abdominal CT findings were detected in 240 (20.3%) and 328 (27.7%) patients, respectively. In 147 patients (12.4%), intra-abdominal malignancy was present. The most frequent ischemic abdominal CT findings were bowel wall thickening (n = 120; 10.2%) and perivascular infiltration (n = 40; 3.4%). As for non-ischemic findings, colitis (n = 91; 7.7%) and small bowel inflammation (n = 73; 6.2%) constituted the most frequent disease processes. The duration of hospital stay was found to be higher in patients with abdominal CT findings than in patients without any positive findings (13.8 ± 13 vs. 10.4 ± 12.8 days, P < 0.001). The frequency of abdominal CT findings was significantly higher in patients who did not survive the infection than in patients who were discharged after recovery (41.7% vs. 27.4%, P < 0.001). Increased AA-CAS was found to be associated with a higher risk of ischemic conditions in abdominal CT examinations. CONCLUSION Abdominal symptoms in patients with COVID-19 are usually associated with positive CT findings. The presence of ischemic findings on CT correlates with poor COVID-19 outcomes. A high AA-CAS is associated with abdominal ischemic findings in patients with COVID-19