 |
 |
 |
 |
 |
 |
Sains Malaysiana 47(12)(2018): 3077–3084 http://dx.doi.org/10.17576/jsm-2018-4712-18
Current Progress in Production of Flavonoids
using Systems and Synthetic Biology Platforms
(Kajian Semasa dalam Penghasilan Flavonoid
menggunakan Teknik Biologi Sistem dan Biologi Sintetik)
KU NURUL AQMAR KU BAHAUDIN1, SURIANA SABRI2,3, AHMAD BAZLI RAMZI1, ADAM LEOW THEAN CHOR2,4, TEWIN TENCOMNAO5 & SYARUL NATAQAIN BAHARUM1*
1Institute of Systems Biology (INBIOSIS), Universiti
Kebangsaan Malaysia, 43600 UKM Bangi, Selangor Darul Ehsan, Malaysia
2Enzyme and Microbial Technology Research
Center, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra
Malaysia, 43400 Serdang, Selangor Darul Ehsan, Malaysia
3Department of Microbiology, Faculty of
Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400
Serdang, Selangor Darul Ehsan, Malaysia
4Department of Cell and Molecular Biology, Faculty of
Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400
Serdang, Selangor Darul Ehsan, Malaysia
5Department of Clinical Chemistry, Faculty of Allied Health
Sciences, Chulalongkorn University, Bangkok, Thailand
Diserahkan: 14 September 2018/Diterima:
14 September 2018
ABSTRACT
Flavonoid is an
industrially-important compound due to its high pharmaceutical and
cosmeceutical values. However, conventional methods in extracting and
synthesizing flavonoids are costly, laborious and not sustainable due to small
amount of natural flavonoids, large amounts of chemicals and space used.
Biotechnological production of flavonoids represents a viable and sustainable
route especially through the use of metabolic engineering strategies in
microbial production hosts. In this review, we will highlight recent strategies
for the improving the production of flavonoids using synthetic biology
approaches in particular the innovative strategies of genetically-encoded
biosensors for in vivo metabolite analysis and high-throughput screening
methods using fluorescence-activated cell sorting (FACS).
Implementation of transcription factor based-biosensor for microbial flavonoid
production and integration of systems and synthetic biology approaches for
natural product development will also be discussed.
Keywords: Biosensor; flavonoid;
metabolic engineering; microbial systems; synthetic biology
ABSTRAK
Flavonoid merupakan sebatian penting
secara industri disebabkan oleh permintaannya yang tinggi dalam
farmaseutik dan mempunyai nilai kosmeseutik. Walau bagaimanapun,
kebiasaannya kaedah pengekstrakan dan sintesis flavonoid adalah
berkos tinggi, rumit dan tidak mapan disebabkan oleh penghasilan
flavonoid semula jadi yang rendah. Selain itu, kaedah ini juga
menggunakan ruang makmal yang besar dan bahan kimia dalam kuantiti
yang banyak. Hasil pengeluaran bioteknologi daripada flavonoid
menunjukkan berdaya maju dan laluan yang mapan. Ini dapat dilihat
melalui pelbagai kaedah yang digunakan di dalam kejuruteraan metabolik
dan biologi sintetik dengan menggunakan mikrob sebagai hos bagi
pengeluaran hasil produk. Di dalam ulasan kajian ini, kami akan
mengetengahkan kaedah bagi meningkatkan penghasilan flavonoid
menggunakan teknik biologi sintetik. Melalui kaedah ini, teknik
biosensor berasaskan pengekod genetik yang digunakan bagi menganalisis
metabolit secara in vivo dan kaedah saringan daya pemprosesan tinggi berasaskan
pengisihan sel teraktif berpendarfluor (FACS). Oleh yang demikian, penggunaan
bioteknologi terhadap penghasilan flavonoid pada masa kini menggunakan
pendekatan integrasi antara biologi sistem dan biologi sintetik
bagi perkembangan produk semula jadi akan dibincangkan dengan
lebih lanjut.
Kata
kunci: Biologi sintetik; biosensor; flavonoid; kejuruteraan metabolisme;
sistem mikrob RUJUKAN
Ahmad, R.,
Sahidin, I., Taher, M., Low, C., Noor, N.M., Sillapachaiyaporn, C.,
Chuchawankul, S., Temcomnao, T., Iskandar, F., Rajab, N.F. & Baharum, S.N.
2018. Polygonumins A, a newly isolated compound from the stem of Polygonum
minus Huds with potential medicinal activities. Scientific Reports 8(1):
4202.
Bailey, J.E.
1991. Towards a science of metabolic engineering. Science 252(5013):
1668-1675.
Bakhtiari,
M., Panahi, Y., Ameli, J. & Darvishi, B. 2017. Protective
effects of flavonoids against Alzheimer's disease related neural
dysfunctions. Biomedicine and Pharmotherapy 93: 218-229.
Carletti,
G., Nervo, G. & Cattivelli, L. 2014. Flavonoids and melanins: A common
strategy across two kingdoms. International Journal of Biological Sciences 10(10):
1159.
Celli, G.B.,
Ghanem, A. & Brooks, M.S.L. 2015. Optimization of ultrasound-assisted
extraction of anthocyanins from haskap berries (Lonicera caerulea L.)
using response surface methodology. Ultrasonics Sonochemistry 27:
449-455.
Chou, H.H.
& Keasling, J.D. 2013. Programming adaptive control to evolve increased
metabolite production. Nature Communications 4: 2595-2603.
Costa, S.L.,
Silva, V.D.A., dos Santos Souza, C., Santos., C.C., Paris, I., Muñoz, P. &
Segura-Aguilar, J. 2016. Impact of plant-derived flavonoids on neurodegenerative
diseases. Neurotoxicity Research 30(1): 41-52.
David, F.,
Nielsen, J. & Siewers, V. 2016. Flux control at the malonyl-CoA node
through hierarchical dynamic pathway regulation in Saccharomyces cerevisiae. ACS Synthetic Biology 5(3): 224-233.
De Castro,
M.L. & Garc?a-Ayuso, L.E. 1998. Soxhlet extraction of solid materials: An
outdated technique with a promising innovative future. Analytica Chimica
Acta 369(1): 1-10.
Djouossi, M.G., Ngnokam, D.,
Kuiate, J.R., Tapondjou, L.A., Harakat, D. & Voutquenne-Nazabadioko, L.
2015. Antimicrobial and antioxidant flavonoids from the leaves of Oncoba
spinosa Forssk. (Salicaceae). BMC Complementary and Alternative
Medicine 15(1): 134.
Diamond, A.
& Desgagne-Penix, I. 2015. Metabolic engineering for the production of
plant isoquinoline alkaloids. Plant Biotechnology Journal: 1319-1328.
Elowitz,
M.B. & Leibler, S. 2000. A synthetic oscillatory network of transcriptional
regulators. Nature 403(6767): 335-338.
Ezhilarasi,
A.A., Vijaya, J.J., Kaviyarasu, K., Maaza, M., Ayeshamariam, A. & Kennedy,
L.J. 2016. Green synthesis of NiO nanoparticles using Moringa oleifera extract
and their biomedical applications: Cytotoxicity effect of nanoparticles against
HT-29 cancer cells. Journal of Phytochemistry and Photobiology B: Biology 164:
352-360.
Farrow,
S.C., Hagel, J.M., Beaudoin, G.A.W., Burns, D.C. & Facchini, P.J. 2015.
Stereochemical inversion of (S)-reticuline by a cytochrome P450 fusion in opium
poppy. Nature Chemical Biology 11(9): 728-732.
Frabasile,
S., Koishi, A.C., Kuczera, D., Silveira, G.F., Verri, W.A., Dos
Santos, C.N.D. & Bordignon, J. 2017. The citrus flavanone
naringenin impairs dengue virus replication in human cells. Scientific
Reports p. 7. Galanie, S.,
Thodey, K., Trenchard, I.J., Filsinger Interrante, M. & Smolke, C.D. 2015.
Complete biosynthesis of opioids in yeast. Science 349(6252): 1095-1100.
Gardner,
T.S., Cantor, C.R. & Collins, J.J. 2000. Construction of a genetic toggle
switch in Escherichia coli. Nature 403(6767): 339-342.
Gibson,
D.G., Benders, G.A., Axelrod, K.C., Zaveri, J., Algire, M.A., Moodie, M.,
Montague, M.G., Venter, J.C., Smith, H.O. & Hutchison, C.A. 2008. One-step
assembly in yeast of 25 overlapping DNA fragments to form a complete synthetic Mycoplasma
genitalium genome. Proceedings of the National Academy of Sciences 105(51):
20404-20409.
Gibson,
D.G., Glass, J.I., Lartigue, C., Noskov, V.N., Chuang, R.Y., Algire, M.A.,
Benders, G.A., Montague, M.G., Ma, L., Moodie, M.M., Merryman, C., Vashee, S.,
Krishnakumar, R., Assad-Garcia, N., Andrews-Pfannkoch, C., Denisova, E.A.,
Young, L., Qi, Z.Q., Segall-Shapiro, T.H., Calvey, C.H., Parmar, P.P.,
Hutchison, C.A., Smith, H.O. & Venter, J.C. 2010. Creation of a bacterial
cell controlled by a chemically synthesized genome. Science 329(5987):
52-56.
Global
Flavonoids Market will reach USD 1047.63 million in 2021: Zion Market Research.
(2016, December 19). Retrieved from
http://www.econotimes.com/Global-Flavonoids-
Market-will-reach-USD-104763-million-in-2021-Zion- Market-Research-457514.
Hwang, E.I.,
Kaneko, M., Ohnishi, Y. & Horinouchi, S. 2003. Production of plant-specific
flavanones by Escherichia coli containing an artificial gene cluster. Applied
and Environmental Microbiology 69(5): 2699-2706.
Jamaluddin,
D., Normah, M.N. & Goh. H.H. 2017. Transcriptome analysis of Carica
papaya embryogenic callus upon De-etiolated 1 (DET1) gene suppression. Genomics
Data 12: 120-121.
Jang, S.,
Jang, S., Xiu, Y., Kang, T.J., Lee, S.H., Koffas, M.A.G. & Jung, G.Y. 2017.
Development of artificial riboswitches for monitoring of Naringenin in vivo. ACS Synthetic Biology 6(11): 2077-2085.
Jiang, H.,
Wood, K.V. & Morgan, J.A. 2005. Metabolic engineering of the
phenylpropanoid pathway in Saccharomyces cerevisiae. Applied and
Environmental Microbiology 71(6): 2962-2969.
Jovanović,
A.A., Đorđević, V.B., Zdunić, G.M.,
Pljevljakušić, D.S., Šavikin, K.P., Gođevac, D.M. &
Bugarski, B.M. 2017. Optimization of the extraction process of polyphenols from Thymus serpyllum L. herb using maceration, heat-and-ultrasound-assisted
techniques. Separation and Purification Technology 179: 369-380.
Khairudin,
K., Sukiran, N.A., Goh, H.H., Baharum, S.N. & Normah, M.N. 2014. Direct
discrimination of different plant populations and study on temperature effects
by Fourier transform infrared spectroscopy. Metabolomics 10(2): 203-
211.
Ko, K.P.,
Kim, C.S., Ahn, Y., Park, S.J., Kim, Y.J., Park, J.K., Lim, Y.K., Yoo, K.Y.,
Yoo, K.Y. & Kim, S.S. 2015. Plasma isoflavone concentration is associated
with decreased risk of type 2 diabetes in Korean women but not men: Results
from the Korean genome and epidemiology study. Diabetologia 58: 726-735.
Korn, M.,
Peterek, S., Mockk, H.P., Heyer, A.G. & Hincha, D.K. 2008. Heterosis in the
freezing tolerance, and sugar and flavonoid contents of crosses between Arabidopsis
thaliana accessions of widely varying freezing tolerance. Plant, Cell
& Environment 31(6): 813-827.
Lander, E.S.
2016. The heroes of CRISPR. Cell 164(1): 18-28. Lani, R.,
Hassandarvish, P., Shu, M.H., Phoon, W.H., Chu, J.J.H., Higgs, S.,
Vandalingham, D., Abu Bakar, S. & Zandi, K. 2016. Antiviral activity of
selected flavonoids against Chikungunya virus. Antiviral Research 133:
50-61.
Leonard, E.,
Lim, K.H., Saw, P.N. & Koffas, M.A. 2007. Engineering central metabolic
pathways for high-level flavonoid production in Escherichia coli. Applied
and Environmental Microbiology 73(12): 3877-3886.
Li, S., Si,
T., Wang, M. & Zhao, H. 2015. Development of a synthetic malonyl-CoA sensor
in Saccharomyces cerevisiae for intracellular metabolite monitoring and
genetic screening. ACS Synthetic Biology 4(12): 1308-1315.
Liang, W.F.,
Cui, L.Y., Cui, J.Y., Yu, K.W., Yang, S., Zhang, C. & Xing, X.H. 2017.
Biosensor-assisted transcriptional regulator engineering for Methylobacterium
extorquens AM1 to improve mevalonate synthesis by increasing the acetyl-
CoA supply. Metabolic Engineering 39: 159-168.
Lim, H.J.,
Nguyen, T.T.H., Kim, N.M., Park, J.S., Jang, T.S. & Kim, D. 2017.
Inhibitory effects of flavonoids against NS2B-NS3 protease of ZIKA virus and
their structure activity relationship. Biotechnology Letters 39(3):
415-421.
Liu, Y.,
Zhuang, Y., Ding, D., Xu, Y., Sun, J. & Zhang, D. 2017. Biosensor-based
evolution and elucidation of a biosynthetic pathway in Escherichia coli. ACS Synthetic Biology 6(5): 837-848.
Loke, K.K.,
Rahnamaie-Tajadod, R., Yeoh, C.C., Goh, H.H., Mohamed-Hussein, Z.A., Zainal,
Z., Ismail, I. & Noor, N.M. 2017. Transcriptome analysis of Polygonum
minus reveals candidate genes involved in important secondary metabolic pathways
of phenylpropanoids and flavonoids. PeerJ 5: e2938.
Lovegrove,
J.A., Stainer, A. & Hobbs, D.A. 2017. Role of flavonoids and nitrates in
cardiovascular health. Proceedings of the Nutrition Society 76(2):
83-95.
Marienhagen,
J. & Bott, M. 2013. Metabolic engineering of microorganisms for the
synthesis of plant natural products. Journal of Biotechnology 163(2):
166-178.
Mahr, R.
& Frunzke, J. 2016. Transcription factor-based biosensors in biotechnology:
Current state and future prospects. Applied Microbiology and Biotechnology 100(1):
79-90.
Mahr, R., von Boeselager,
R.F., Wiechert, J. & Frunzke, J. 2016. Screening of an Escherichia coli promoter
library for a phenylalanine biosensor. Applied Microbiology and
Biotechnology 100(15): 6739-6753.
Martin, V.J.J., Piteral, D.J., Withers, S.T., Newman, J.D.
& Keasling, J.D. 2003. Engineering a mevalonate pathway in Escherichia
coli for production of terpenoids. Nature Biotechnology 21(7):
796-802.
Mohamed, A.N., Vejaya,
J. & Yusoff, M.M. 2015. Review on Eurycoma longifolia pharmacological
and phytochemical properties. Journal of Applied Sciences 15(6): 831.
Ng, Y.P., Or, T.C.T.
& Ip, N.Y. 2015. Plant alkaloids as drug leads for Alzheimer’s disease. Neurochemistry
International 89: 260-270.
Nielsen, J. &
Keasling, J.D. 2011. Synergies between synthetic biology and metabolic
engineering. Nature Biotechnology 29(8): 693-695.
Pariyani, R., Ismail,
I.S., Azam, A., Khatib, A., Abas, F., Shaari, K. & Hamza, H. 2017. Urinary
metabolic profiling of cisplatin nephrotoxicity and nephroprotective effects of Orthosiphon stamineus leaves elucidated by 1H NMR spectroscopy. Journal
of Pharmaceutical and Biomedical Analysis 135: 20-30.
Park, H.J., Choi, Y.J.,
Lee, J.H. & Nam, M.J. 2017. Naringenin causes ASK1-induced apoptosis via
reactive oxygen species in human pancreatic cancer cells. Food and Chemical
Toxicology 99: 1-8.
Peng, Y., Xuan, M.,
Leung, V.Y.L. & Cheng, B. 2015. Stem cells and aberrant signalling of
molecular systems in skin aging. Ageing Research Reviews 19: 8-21.
Peralta-Yahya, P.P.,
Ouellet, M., Chan, R., Mukhopadhyay, A., Keasling, J.D. & Lee, T.S. 2011.
Identification and microbial production of a terpene-based advanced biofuel. Nature
Communications 27(2): 483-494.
Rai, A., Saito, K. &
Yamazaki, M. 2017. Integrated omics analysis of specialized metabolism in
medicinal plants. Plant Journal 90(4): 764-787.
Rasines-Perea, Z. &
Teissedre, P.L. 2017. Grape polyphenols’ effects in human cardiovascular
diseases and diabetes. Molecules 22(1): E68.
Ro, D.K., Paradise,
E.M., Ouellet, M., Fisher, K.J., Newman, K.L., Ndungu, J.M., Ho, K.A., Eachus,
R.A., Ham, T.S., Kirby, J., Chang, M.C., Withers, S.T., Shiba, Y., Sarpong, R.
& Keasling, J.D. 2006. Production of the antimalarial drug precursor
artemisinic acid in engineered yeast. Nature 440(7086): 940.
Rodriguez, A., Strucko,
T., Stahlhut, S.G., Kristensen, M., Svenssen, D.K., Forster, J., Nielsen, J.
& Borodina, I. 2017. Metabolic engineering of yeast for fermentative
production of flavonoids. Bioresource Technology 245: 1645-1654.
Rodriguez, A.,
Kildegaard, K.R., Li, M., Borodina, I. & Nielsen, J. 2015. Establishment of
a yeast platform strain for production of p- coumaric acid through metabolic
engineering of aromatic amino acid biosynthesis. Metabolic Engineering 31:
181-188.
Rogers, J.K. &
Church, G.M. 2016. Genetically encoded sensors enable real-time observation of
metabolite production. Proceedings of the National Academy of Sciences 113(9):
2388-2393.
Rogers, J.K., Taylor,
N.D. & Church, G.M. 2016. Biosensor-based engineering of biosynthetic
pathways. Current Opinion in Biotechnology 42: 84-91.
Rogers, J.K., Guzman,
C.D., Taylor, N.D., Raman, S., Anderson, K. & Church, G.M. 2015. Synthetic
biosensors for precise gene control and real-time monitoring of metabolites. Nucleic
Acids Research 43(15): 7648-7660.
Rusdi, N.A., Goh, H.H.
& Baharum, S.N. 2016. GC-MS/ Olfactometric characterisation and aroma
extraction dilution analysis of aroma active compounds in ‘Polygonum minus’
essential oil. Plant Omics 9(4): 289.
Saewan, N. &
Jimtaisong, A. 2015. Natural products as photoprotection. Journal of
Cosmetic Dermatology 14(1): 47-63.
Scervino, J.M., Ponce,
M.A., Erra-Bassells, R., Vierheilig, H., Ocampo, J.A. & Godeas, A. 2005.
Flavonoids exhibit fungal species and genus specific effects on the
presymbiotic growth of Gigaspora and Glomus. Mycological Research 109(7):
789-794.
Sharifi, N., Mahernia,
S. & Amanlou, M. 2017. Comparison of different methods in quercetin
extraction from leaves of Raphanus sativus L. Pharmaceutical Sciences 23(1): 59-65.
Siedler, S., Khatri,
N.K., Zsohár, A., Kjærbølling, I., Vogt, M., Hammar, P., Nielsen, C.F.,
Mariehagen, J., Sommer, M.O.A. & Joensson, H.N. 2017. Development of a
bacterial biosensor for rapid screening of yeast p-coumaric acid production. ACS
Synthetic Biology 6(10): 1860-1869.
Siedler, S., Stahlhut,
S.G., Malla, S., Maury, J.Ô. & Neves, A.R. 2014. Novel biosensors based on
flavonoid-responsive transcriptional regulators introduced into Escherichia
coli. Metabolic Engineering 21: 2-8.
Skjoedt, M.L., Snoek,
T., Keldegaard, K.R., Arsovska, D., Eichenberger, M., Geodecke, T.J., Rajkumar,
A.S., Zhang, J., Kristensen, M., Lehka, B.J., Siedler, S., Borodina, I.,
Jensen, M.K. & Keasling, J.D. 2016. Engineering prokaryotic transcriptional
activators as metabolite biosensors in yeast. Nature Chemical Biology 12(11):
951-958.
Stahlhut, S.G., Siedler,
S., Malla, S., Harrison, S.J., Maury, J., Neves, A.R. & Forster, J. 2015.
Assembly of a novel biosynthetic pathway for production of the plant flavonoid
fisetin in Escherichia coli. Metabolic Engineering 31: 84-93.
Thuan, N.H., Malla, S.,
Trung, N.T., Dhakal, D., Pokhrel, A.R., Chu, L.L. & Sohng, J.K. 2017.
Microbial production of astilbin, a bioactive rhamnosylated flavononol, from
taxifolin. World Journal of Microbiology and Biotechnology 33(2): 36.
Triantafyllidi, A.,
Xanthos, T., Papalois, A. & Triantafillidis, J.K. 2015. Herbal and plant
therapy in patients with inflammatory bowel disease. Annals of
Gastroenterology: Quarterly Publication of the Hellenic Society of
Gastroenterology 28(2): 210.
Watanabe, M. &
Ayugase, J. 2015. Effect of low temperature on flavonoids, oxygen radical
absorbance capacity values and major components of winter sweet spinach (Spinacia
oleracea L.). Journal of the Science of Food and Agriculture 95(10):
2095-2104.
Watts, K.T., Lee, P.C.
& Schmidt-Dannert, C. 2004. Exploring recombinant flavonoid biosynthesis in
metabolically engineered Escherichia coli. Chembiochem 5(4):
500-507.
Xiong, D., Lu, S., Wu,
J., Liang, C., Wang, W., Wang, W., Jin, J.M. & Tang, S.Y. 2017. Improving
key enzyme activity in phenylropanoid pathway with a designed biosensor. Metabolic
Engineering 40: 115-123.
Yan, Y., Kohli, A. &
Koffas, M.A. 2005. Biosynthesis of natural flavanones in Saccharomyces
cerevisiae. Applied and Environmental Microbiology 71(9): 5610-5613.
Youns, M. & Hegazy, W.A.H. 2017. The
natural flavonoid fisetin inhibits cellular proliferation of hepatic,
colorectal, and pancreatic cancer cells through modulation of multiple
signalling pathway. PloS One 12(1): e0169335.
*Pengarang untuk
surat-menyurat; email: nataqain@ukm.edu.my
|
|||
|
