Supervisions

Ms. Aimi Aishah Ariffin

Title: Production of Citronellol as an Artificial Flavour using Whole-Cell Saccharomyces cerevisiae: Design of a Continuous Closed-Gas-Loop Bioreactor fro Biotransformation.

Research Summary

I am interested in the application of the technique of a continuous closed-gas-loop bioreactor for biotransformation (CCGLBB) of geraniol to citronellol using baker’s yeast, Saccharomyces cerevisiae. The advantages involving this technique include: (i) in situ product removal, thus eliminates downstream processes such as centrifugation and filtration, (ii) problem of solubility with substrate and product do not exist, (iii) diffusion in the gas phase is more efficient than in solution, thus provides efficient mass transfer of substrate to biocatalyst; and (iv) substrate inhibition can be avoided during biotransformation. The aim of this work is to construct a high performance of yeast in a CCGLBB with high product yield (citronellol) with less or no formation of side-products. Throughout this work, biotransformation using both growing and non-growing cells of baker’s yeast will be applied. These two types of methods will be investigated as the conditions of yeast growth and biotransformation are different. The optimum conditions between these two will be sought out. Parameters that will be carried out are pH, temperature, substrate flow rate and stirring speed.

Mr. Mohd Rezuan M. Aspar

Title: Enhancing the Biocatalytic Performance of Stereospecific Biotransformation of Geraniol into Citronellol using Genetically Engineered Baker’s Yeast Type-II, Saccharomyces cerevisiae.

Research Summary

My current research work is mainly on the genetic engineering approach for the biocatalytic production of citronellol, a highly potential artificial compound used as flavours and fragrances in food industries. This innovative strategy that emerged from the development of molecular biology and genetic engineering technology will be used to engineer an E.coli strain overexpressing YADH protein, an enzyme used as a biocatalyst for the bioconversion of geraniol into citronellol. In this project, the gene encoding YADH protein will be extracted from the yeast and inserted into the genome of an E.coli strain used as the host, so as to obtain the over-expression of YADH enzyme during the shake flask fermentation of the engineered E.coli with geraniol as the substrate. Since this bacterial strain is more easily- and fastly- growing compared to the yeast, the production of citronellol is expected to be significantly increased in comparison with the level achieved via the previous method.

Ms. Fatimatul Zaharah Abas

Title: Asymmetric Synthesis and Separation of a Coupled Enzyme-Catalysed Production of Drug Precursor.

Research Summary

I am keenly interested at come across to the research of the production of drug precursor from Enzyme-Catalyzed Asymmetric by using a novel membrane biorecator. The synthesizing of drug precursor is very important in order to produce the angotensin-converting enzyme (ACE) inhibitor which is known as an antihypertensive drug that used for cardiovascular diseases treatment. This enzyme will help in blocking the formation of angiotensin in the kidney, which leading to the relaxation of the arteries.ACE inhibitors are a group of pharmaceuticals that are used primarily in treatment of hypertension and congestive heart failure, in some cases as the drugs of first choice. This also lead it to be the first-line as several agents in the class have been clinically shown to be superior to other classes of drugs in the reduction of morbidity and mortality.There are two types of building blocks of ACE inhibitors which are (S)-2-amino-4-phenylbutanoic acid and (R)-2-hydroxy-4-phenylbutanoic acid. Since the S configuration is about 100 times more active than R configuration, that (S)-2-amino-4-phenylbutanoic acid is proposed for ACE inhibitors synthesis. This enzymatic synthesis can be performed through an asymmetric synthesis which is allows the production of one enantiomer at up to 100% yield. As well the synthesis of ACE inhibitor drug precursor via this enzymatic synthesis requires reduced nicotinamide adenine dinucleotide (NADH). Since NADH is expensive, an efficient and cost-effective in situ regeneration from the oxidized form of NAD+ is prerequisite for large scale applications in order to meet economic constraints. For this research project, the usage of novel membrane bioreactor design is believed will help in optimizing the profit and reducing the costs since it features a process of simultaneous reaction and also in situ product removal which is allow a high degree of operating flexibility and it also could be readily adapted for the benefit of the people over the world.

Mr. Fadzil Noor Bin Gonawan

Title: Production of (S)-Ibuprofen acid in Pilot Plant Scale: Role of Co-Solvent in The Lumen Side of Enzymatic Membrane Reactor (EMR).

Research Summary

I would like to dedicate my research on production of (S)-Ibuprofen acid via enzymatic membrane reactor. Iso-butyl-propanoic-phenolic acid or know as Ibuprofen belongs to a class of drugs called nonsteroidal anti-inflammatory drug (NSAID) effective in treating fever, pain, and inflammation in the body. Ibuprofen is also the best selling agent for arthritis and represents a billion-dollar-a-year market. It is currently being sold as racemic compound which is a mixture of (R,S)-enantiomers. However only the (S)-enantiomer of ibuprofen provides the desired therapeutic (healing) effect, while the other enantiomer is inactive and causes side effects. The (S)-ibuprofen acid is a low-volume and yet high-value product. Enzymatic membrane reactor (EMR) for chiral drugs synthesis has high potential to be commercializing among others chiral drug separation technology. EMR has been reported to overcome some of the limitations of the conventional system. An enzymatic membrane reactor allows hydrolysis reaction of racemic ester and selective separation of the product simultaneously which enhance product conversion. Lipase from candida rugosa has been used as a biocatalyst for the resolution of racemic esters and alcohols, as it acts enantioelectively and prefers to catalyze the synthesis of one of the enantiomers using hydrolysis with higher preference. The biocatalyst was immobilized in the membrane pore with controlled constant trans-membrane pressure (TMP) as a border between shell and lumen side of the enzymatic membrane reactor. The reaction will occur at the surface of the membrane, while the biocatalyst allowing only certain product (S-ibuprofen acid) to diffuse into the lumen side of the membrane.  In order to break through the challenge towards realization of (S)-ibuprofen production plant, study on pilot plant scale must be done. The study will enhance and optimizing the production of (S)-ibuprofen in pilot plant scale by focusing on role of co-solvent in aqueous phase in the lumen side of the reactor. Hopefully the co-solvent being used will increase the solubility of (S)-ibuprofen in aqueous phase, hence simplified downstream processing of the enzymatic membrane reactor.

1) Postgraduates:

Main Supervision:

1. Ms. Aimi Aishah Ariffin (MSc.) – (Graduated)
   Title: Kinetics of Biotransformation for Citronellol Production Using Saccharomyces cerevisiae.
2. Ms. Nazira Mahmud (MSc.) – (Graduated)
   Title: Production of a-terpeniol From the Citrus sinensis Peel Extract Using Biotransformation.
3. Ms. Khor Guat Kheng (MSc.) – (Graduated)
   Title: The Biotransformation of cis/trans 3,7-dimethyl-2,6-octadien-1-ol Mediated by Saccharomyces cerevisiae.
4. Ms. Fatimatul Zaharah Abas (MSc.) – (Submitted)
   Title: Optimising the Production of Chiral Alcohol for Angiotensin Receptor Blocker (ARB) Synthesis via Aspergillus niger-Catalysed Biotransformation of 1-4-Bromo-phenyl-ethanone.
5. Mr. Mohd Fadzil Gonawan (MSc.) – (On-going)
   Title: The Effect of Different Solvent on the Downstream Process of S-Ibuprofen Production.
6. Mr. Lau Sie Yon (PhD.) – (On-going)
   Title: Modelling and Simulation of Membrane Bioreactor for S-Ibuprofen Production Pilot Plant.
7. Mr. Adib Zubaidi (MSc.) – (On-going)
   Title: Determination of a Specific Reductase Protein for the Conversion of Geraniol to Citronellol.
8. Ms. Nor Naimah Rosyadah Ahmad (MSc.) – (On-going)
   Title: Study on Mass-Transfer Rate of Nutrient Through Nano CaCO3 Coated Fertilizer.

Co-Supervision:

1. Mrs. Noor Fazliani Shoparwe (MSc.) – (Graduated)
2. Ms. Nazira Khabibor Rahman (MSc.) – (Graduated)
3. Ms. Noor Aziah Serri (PhD.) – (On-going)
4. Ms. Eka Anggraini Azuardi (MSc.) – (On-going)

2) Undergraduates:

Final Year Research Projects:

2006:

1. Norhazrina Jamil: Equilibrium, kinetics and mechanism for the sorption of methylene blue onto S. zalacca’s skin.
2. Sani Abdul Salam: Application of aqueous 2-phase for protein separation: Polyethylene glycol-Magnesium sulphate.
3. Foo Ai Ling: Aqueous 2-phase extraction of glycoprotein from Artocarpus integrifolia seeds: Design of experiment and optimisation.
4. Vincent Lau Bick Yeong: Aqueous 2-phase system for protein separation: Polyethylene glycol/ammonium sulphate.
5. Lim Ching Yee: Aqueous 2-phase system for protein separation: Sodium carbonate with polyethylene glycol.

2007:

1. Ngo Jin Kion: Kinetic investigation of a stereospecific addition biotransformation of geraniol using a non-growing Sacchromyces cerivisiae under controlled conditions.
2. Aimi Aishah Arifin: A chemospecific enzyme-catalysed ring-opening-polymerisation reaction (ROP) of lactone forming poly--caprolactone in a non-aqueous medium.
3. Mohd Reza Mohd Rodzi: On the stability study of an exothermic biocatalytic reaction and its application in control systems.
4. Chew Chia Yang: On the stability of an enzyme-catalysed bioconversion with feedback inhibition: from dynamics and control perspectives.

2008:

1. H’ng Jia Ling: On the effect of cell immobilisation towards geraniol biotransformation.
2. Fadhila Hasanah Ahmad Nadzri: A preliminary study of gaseous stereospecific biotransformation of geraniol in a bed of non-growing Saccharomyces cerevisiae.
3. Chew Chan Yoke: A bench-scale bioconversion of gaseous geraniol forming citronellol in a growing Saccharomyces cerevisiae with an in situ product removal.
4. Lily Elissa Zakaria: On the effect of whole-cell bioconversion towards the cellular activity of Saccharomyces cerevisiae.

2009:

1. Nazeyra Fadzaauny: On the extraction and direct stereospecific biotransformation of (+)-citronellal to (-)-isopulegol using the whole Saccharomyces cerevisiae cells.
2. Shiraz Yusuf Patel Dawoodi: In-situ fermentation and stereospecific transformation of geraniol using a continuous-closed-gas-loop bioreactor for biotransformation.
3. Lim Guat Mei: On the stability and bifurcation studies of a coupled jacketed continuous stirred tank chemical reactor (CSTR).
4. Tan Yong Nian: Investigating the rate of nutrient diffusion through a cellular membrane: A case study on the membrane of Escherichia coli.

2010:

1. Gopal Paramesivam: On the Need of Nutrient Concentration on the Growth of Saccharomyces cerevisiae During a Stereospecific Biotransformation
2. Haaziq Zahar: Taming the Wild-Type Aspergillus niger on the Bioreduction of 1,4-bromo-phenyl-ethanone into (R)-1-4-bromophenyl ethanol in the Production of Angiotensin Receptor Blocker, (ARB) Chiral Drug Precursor.
3. Tam Sau Ying: Investigating the Optimum Parameters of cis-3,7-dimethyl-trans-2-6-octadiene-1-ol Stereospecific Biotransformation in a Single-Phase Process.
4. Norhayati Abdul Hamid: On the Study of Mass Transfer Effect Towards the Baker’s Yeast Type-II-Mediated Stereospecific Biotransformation of 3,7-dimethyl-trans-2-6-octadiene-1-ol to 3,7-dimethyloct-6-en-1-ol in a Continuous-Closed-Gas-Loop Bioreactor for Biotransformation.

2011:

1. Mohd Shaharolnaim B. Safaruddin,: Improvement of Cation Exchange Capacity (CEC) Sample Sericite from Bidor with Hydrothermal Method.
2. Yeoh Hooi Keng: Competition between Two Species of Algae: Experimental & Modelling Studies.