Synthetic biology and food manufacturing

doi:10.12211/2096-8280.2020-005

Abstract

Abstract:

As global environmental pollution intensifies, climate continues to change, and population continues to grow, how to ensure safe, nutritious and sustained food supply faces huge challenges. These challenges put forward new requirements for the future food supply and function. Using synthetic biology technologies to create cell factories applicable in the food industry to convert renewable raw materials into important food components, functional food additives and nutritional chemicals is an important way to solve the problems facing the food industry. This article first introduces the importance of synthetic biology to the innovation and breakthroughs in the field of food manufacturing. Secondly, taking artificial food, plant natural products and human milk oligosaccharide, three typical food products from biological manufacturing, as examples, the current tasks and challenges of food synthetic biology are discussed. Finally, the development trends of synthetic biology and food manufacturing in China are summarized and prospected. By strengthening the development and application of food synthetic biology and the related food biotechnologies and being the first to achieve their industrialization, researchers will be able to seize the frontiers of science and technology and industrial highlands globally and benefit mankind.

Key words: synthetic biology, food manufacturing, artificial food, plant natural products, human milk oligosaccharide

摘要：

随着全球环境污染加剧、气候持续变化和人口不断增长，如何保障安全、营养和可持续的食品供给面临巨大挑战。这些挑战对未来食品供给方式和功能提出了新的要求。采用合成生物学技术，创建适用于食品工业的细胞工厂，将可再生原料转化为重要食品组分、功能性食品添加剂和营养化学品是解决食品领域所面临问题的重要途径。本文首先介绍了合成生物学对食品制造领域创新和突破的重要性。其次，以基于合成生物学制造植物蛋白肉所需关键组分、黄酮类植物天然提取物和母乳寡糖这三种典型食品为例，探讨了目前食品合成生物学的任务与挑战。最后，对我国合成生物学与食品制造领域的发展趋势进行了总结和展望。通过加强食品合成生物学等具有重大意义的食品生物技术的开发和应用，开展新食品资源开发和高值利用、多样化食品生产方式变革、功能性食品添加剂和营养化学品制造，并率先实现产业化，将抢占世界科技的前沿和产业高地，造福人类。

关键词: 合成生物学, 食品制造, 人造食品, 植物天然产物, 母乳寡糖

CLC Number:

Q819

Yanfeng LIU, Jingwen ZHOU, Long LIU, Jian CHEN. Synthetic biology and food manufacturing[J]. Synthetic Biology Journal, 2020, 1(1): 84-91.

刘延峰, 周景文, 刘龙, 陈坚. 合成生物学与食品制造[J]. 合成生物学, 2020, 1(1): 84-91.

References 63

1	陈坚. 中国食品科技：从2020到2035[J]. 中国食品学报， 2019， 19(12): 1-5.
	CHEN J. Food Science and technology in China: from 2020 to 2035 [J]. Journal of Chinese Institute of Food Science and Technology, 2019, 19(12):1-5
2	ZHANG G, ZHAO X, LI X, et al. Challenges and possibilities for bio-manufacturing cultured meat[J]. Trends in Food Science & Technology, 2020, 97: 443-450.
3	STEPHENS N, DI SILVIO L, DUNSFORD I, et al. Bringing cultured meat to market: technical, socio-political, and regulatory challenges in cellular agriculture[J]. Trends in Food Science & Technology, 2018. 78: 155-166.
4	SPECHT E A, WELCH D R, REES CLAYTON E M, et al. Opportunities for applying biomedical production and manufacturing methods to the development of the clean meat industry[J]. Biochemical Engineering Journal, 2018, 132: 161-168.
5	TUOMISTO H L, TEIXEIRA De Mattos M J. Environmental impacts of cultured meat production[J]. Environmental Science & Technology, 2011, 45(14): 6117-6123.
6	ESHEL G, SHEPON A, MAKOV T, et al. Land, irrigation water, greenhouse gas, and reactive nitrogen burdens of meat, eggs, and dairy production in the United States[J]. PNAS, 2014, 111(33): 11996-12001.
7	BHAT Z F, KUMAR S, FAYAZ H. In vitro meat production: challenges and benefits over conventional meat production[J]. Journal of Integrative Agriculture, 2015, 14(2): 241-248.
8	POST M J. Cultured meat from stem cells: Challenges and prospects[J]. Meat Science, 2012, 92(3):297-301.
9	LIU S, WANG M, DU G, et al. Improving the active expression of transglutaminase in Streptomyces lividans by promoter engineering and codon optimization[J]. BMC Biotechnology, 2016, 16:75.
10	LIU S, WAN D, WANG M, et al. Overproduction of pro-transglutaminase from Streptomyces hygroscopicus in Yarrowia lipolytica and its biochemical characterization[J]. BMC Biotechnology, 2015, 15:75.
11	CALLEJON S, SENDRA R, FERRER S, et al. Recombinant laccase from Pediococcus acidilactici CECT 5930 with ability to degrade tyramine[J]. PLoS One, 2017, 12(10). DOI: 10.1371/journal.pone.0186019. DOI
12	BHOKISHAM N, PAKHCHANIAN H, QUAN D, et al. Modular construction of multi-subunit protein complexes using engineered tags and microbial transglutaminase[J]. Metabolic Engineering, 2016. 38: 1-9.
13	VIDYA J, SAJITHA S, USHASREE M V, et al. Genetic and metabolic engineering approaches for the production and delivery of L-asparaginases: an overview[J]. Bioresource Technology, 2017, 245: 1775-1781.
14	FENG Y, LIU S, JIAO Y, et al. Improvement of L-asparaginase thermal stability by regulating enzyme kinetic and thermodynamic states[J]. Process Biochemistry, 2018, 71: 45-52.
15	FENG Y, LIU S, JIAO Y, et al. Enhanced extracellular production of L-asparaginase from Bacillus subtilis 168 by B.subtilis WB600 through a combined strategy[J]. Applied Microbiology and Biotechnology, 2017, 101(4): 1509-1520.
16	NATARAJAN C, JIANG X B, FAGO A, et al. Expression and purification of recombinant hemoglobin in Escherichia coli[J]. PLoS One, 2011, 6(5):e20176.
17	LIU L F, MARTÍNEZ J L, LIU Z H, et al. Balanced globin protein expression and heme biosynthesis improve production of human hemoglobin in Saccharomyces cerevisiae[J]. Metabolic Engineering, 2014, 21: 9-16.
18	MARTÍNEZ J L, LIU L, PETRANOVIC D, et al. Engineering the oxygen sensing regulation results in an enhanced recombinant human hemoglobin production by Saccharomyces cerevisiae[J]. Biotechnology and Bioengineering, 2015, 112(1): 181-188.
19	JIN Y, HE X, ANDOH‐KUMI K, et al. Evaluating potential risks of food allergy and toxicity of soy leghemoglobin expressed in Pichia pastoris[J]. Molecular Nutrition & Food Research, 2018, 62(1): 1700297.
20	ZHAO X, CHOI K R, LEE S Y. Metabolic engineering of Escherichia coli for secretory production of free haem[J]. Nat. Catal., 2018, 1： 720-728.
21	ZHANG J, WENG H, ZHOU Z,et al. Engineering of multiple modular pathways for high-yield production of 5-aminolevulinic acid in Escherichia coli[J]. Bioresource Technology, 2019, 274, 353-360.
22	ZHANG J L, KANG Z, DING W W, et al. Integrated optimization of the in vivo heme biosynthesis pathway and the in vitro iron concentration for 5-aminolevulinate production[J]. Applied Biochemistry and Biotechnology, 2016, 178(6): 1252-1262.
23	ZHANG J, KANG Z, CHEN J, et al. Optimization of the heme biosynthesis pathway for the production of 5-aminolevulinic acid in Escherichia coli [J]. Sci. Rep., 2015, 5:8584.
24	ZHOU J W, DU G C, CHEN J. Novel fermentation processes for manufacturing plant natural products[J]. Current Opinion in Biotechnology, 2014, 25: 17-23.
25	ENGELS B, DAHM P, JENNEWEIN S. Metabolic engineering of taxadiene biosynthesis in yeast as a first step towards Taxol (Paclitaxel) production[J]. Metabolic Engineering, 2008, 10:201-206.
26	GAZAK R, FUKSOVA K, MARHOL P, et al. Preparative method for isosilybin isolation based on enzymatic kinetic resolution of silymarin mixture[J]. Process Biochemistry, 2013, 48:184-189.
27	MAVEL S, DIKIC B, PALAKAS S, et al. Synthesis and biological evaluation of a series of flavone derivatives as potential radioligands for imaging the multidrug resistance-associated protein 1 (ABCC1/MRP1) [J]. Bioorg. Med. Chem., 2006, 14:1599-1607.
28	PADDON C J, WESTFALL P J, PITERA D J, et al. High-level semi-synthetic production of the potent antimalarial artemisinin[J]. Nature, 2013, 496(7446): 528-532
29	MUCHIRI R, WALKER K D. Taxol biosynthesis: tyrocidine synthetase A catalyzes the production of phenylisoserinyl CoA and other amino phenylpropanoyl thioesters[J]. Chem. Biol., 2012, 19:679-685.
30	ZHAO J, LI Q Y, SUN T, et al. Engineering central metabolic modules of Escherichia coli for improving β-carotene production[J]. Metabolic Engineering, 2013, 17:42-50.
31	WANG C, YOON S H, JANG H J, et al. Metabolic engineering of Escherichia coli for a-farnesene production[J]. Metabolic Engineering, 2011, 13:648-655.
32	ASADOLLAHI M A, MAURY J, SCHALK M, et al. Enhancement of farnesyl diphosphate pool as direct precursor of sesquiterpenes through metabolic engineering of the mevalonate pathway in Saccharomyces cerevisiae[J]. Biotechnology Bioengineering, 2010, 106:86-96.
33	RICO J, PARDO E, OREJAS M. Enhanced production of a plant monoterpene by overexpression of the 3-hydroxy-3-methylglutaryl coenzyme a reductase catalytic domain in Saccharomyces cerevisiae[J]. Appl. Environ. Microbiol., 2010, 76:6449-6454.
34	IGNEA C, TRIKKA F, KOURTZELIS I, et al. Positive genetic interactors of HMG2 identify a new set of genetic perturbations for improving sesquiterpene production in Saccharomyces cerevisiae[J]. Microbial Cell Factory, 2012, 11:162.
35	IGNEA C, CVETKOVIC I, LOUPASSAKI S, et al. Improving yeast strains using recyclable integration cassettes, for the production of plant terpenoids[J]. Microbial Cell Factory, 2011, 10:4-22.
36	FISCHER M J C, MEYER S, CLAUDEL P, et al. Metabolic engineering of monoterpene synthesis in yeast[J]. Biotechnology Bioengineering, 2011, 108:1883-1892.
37	SCALCINATI G, KNUF C, PARTOW S, et al. Dynamic control of gene expression in Saccharomyces cerevisiae engineered for the production of plant sesquitepene a-santalene in a fed-batch mode[J]. Metabolic Engineering, 2012, 14:91-103.
38	ZHOU Y J J, GAO W, RONG Q X, et al. Modular pathway engineering of diterpenoid synthases and the mevalonic acid pathway for miltiradiene production[J]. J. Am. Chem. Soc., 2012, 134:3234-3241.
39	LYU Y B, ZENG W Z, DU G C, et al. Efficient bioconversion of epimedin C to icariin by a glycosidase from Aspergillus nidulans[J]. Bioresource Technology, 2019, 289: 121612.
40	LV Y K, XU S, LYU Y B, et al. Engineering enzymatic cascades for the efficient biotransformation of eugenol and taxifolin to silybin and isosilybin[J]. Green Chemistry, 2019, 21(7): 1660-1667.
41	XIU Y, JANG S, JONES J A, et al. Naringenin-responsive riboswitch-based fluorescent biosensor module for Escherichia coli co-cultures[J]. Biotechnology and Bioengineering, 2017, 114(10). DOI: 10.1002/bit. 26340. DOI
42	LV Y K, GAO S, XU S, et al. Spatial organization of silybin biosynthesis in milk thistle Silybum marianum (L.) Gaertn[J]. Plant Journal, 2017, 92(6): 995-1004.
43	LUO Y, LI B Z, LIU D, et al. Engineered biosynthesis of natural products in heterologous hosts[J]. Chemical Society Reviews, 2015, 44(15): 5265-5290.
44	SIEDLER S, STAHLHUT S G, MALLA S, et al. Novel biosensors based on flavonoid-responsive transcriptional regulators introduced into Escherichia coli[J]. Metabolic Engineering, 2014, 21:2-8.
45	CHARBONNEAU M R, O’DONNELL D, BLANTON L V, et al. Sialylated milk oligosaccharides promote microbiota-dependent growth in models of infant undernutrition[J]. Cell, 2016, 164(5): 859-871.
46	ZHANG X, LIU Y, LIU L, et al. Microbial production of sialic acid and sialylated human milk oligosaccharides: advances and perspectives[J]. Biotechnology Advances, 2019, 37(5): 787-800.
47	FAIJES M, CASTEJÓN-VILATERSANA M, VAL-CID C, et al. Enzymatic and cell factory approaches to the production of human milk oligosaccharides[J]. Biotechnology Advances, 2019, 37(5): 667-697.
48	BYCH K, MIKŠ MH, JOHANSON T, et al. Production of HMOs using microbial hosts-from cell engineering to large scale production[J]. Current Opinion in Biotechnology, 2019. 56: 130-137.
49	SPRENGER G A, BAUMGÄRTNER F, ALBERMANN C. Production of human milk oligosaccharides by enzymatic and whole-cell microbial biotransformations[J]. Journal of Biotechnology, 2017, 258:79-91.
50	BODE L, CONTRACTOR N, BARILE D, et al. Overcoming the limited availability of human milk oligosaccharides: challenges and opportunities for research and application[J]. Nutrition Reviews, 2016, 74(10): 635-644.
51	CHOI Y H, PARK B S, SEO J H, et al. Biosynthesis of the human milk oligosaccharide 3-fucosyllactose in metabolically engineered Escherichia coli via the salvage pathway through increasing GTP synthesis and β-galactosidase modification[J]. Biotechnology and Bioengineering, 2019，116: 3324-3332.
52	DROUILLARD S, MINE T, KAJIWARA H, et al. Efficient synthesis of 6'-sialyllactose, 6,6'-disialyllactose, and 6'-KDO-lactose by metabolically engineered E. coli expressing a multifunctional sialyltransferase from the Photobacterium sp. JT-ISH-224[J]. Carbohydr. Res., 2010, 345, 1394-1399.
53	FIERFORT N, SAMAIN E. Genetic engineering of Escherichia coli for the economical production of sialylated oligosaccharides[J]. J. Biotechnol., 2008, 134, 261-265.
54	GUO Y, JERS C, MEYER A S, et al. A Pasteurella multocida sialyltransferase displaying dual trans-sialidase activities for production of 3’-sialyl and 6’-sialyl glycans[J]. J. Biotechnol., 2014, 170: 60-67.
55	HUANG D, YANG K, LIU J, et al. Metabolic engineering of Escherichia coli for the production of 2’-fucosyllactose and 3-fucosyllactose through modular pathway enhancement[J]. Metabolic Engineering, 2017, 41: 23-38.
56	LIU Y F, LIU L, LI J H, et al. Synthetic biology toolbox and chassis development in Bacillus subtilis[J]. Trends in Biotechnology, 2019, 37(5): 548-562.
57	GU Y, XU X H, WU Y K, et al. Advances and prospects of Bacillus subtilis cellular factories: from rational design to industrial applications[J]. Metabolic Engineering, 2018, 50: 109-121.
58	LIU Y F, LI J H, DU G C, et al. Metabolic engineering of Bacillus subtilis fueled by systems biology: recent advances and future directions[J]. Biotechnology Advances, 2017, 35(1): 20-30.
59	ŸZTÜRK S, ŸALIK P, ÖZDAMAR T H. Fed-batch biomolecule production by Bacillus subtilis: a state of the art review[J]. Trends in Biotechnology, 2016， 34(4): 329-345.
60	DIJL J M VAN, HECKER M. Bacillus subtilis: from soil bacterium to super-secreting cell factory[J]. Microbial Cell Factories, 2013， 12(1): 3.
61	DENG J Y, GU L Y, CHEN T C, et al. Engineering the substrate transport and cofactor regeneration systems for enhancing 2'-fucosyllactose synthesis in Bacillus subtilis[J]. ACS Synthetic Biology, 2019, 28(10): 2418-2427.
62	DENG J, CHEN C, GU Y, et al. Creating an in vivo bifunctional gene expression circuit through an aptamer-based regulatory mechanism for dynamic metabolic engineering in Bacillus subtilis[J]. Metabolic Engineering, 2019, 55: 179-190.
63	DONG X, LI N, LIU Z, et al. CRISPRi-guided multiplexed fine-tuning of metabolic flux for enhanced lacto-N-neotetraose production in Bacillus subtilis[J]. Journal of Agricultural and Food Chemistry, 2020, 68(8): 2477-2484.

[1]	Zhidian DIAO, Xixian WANG, Qing SUN, Jian XU, Bo MA. Advances and applications of single-cell Raman spectroscopy testing and sorting equipment [J]. Synthetic Biology Journal, 2023, 4(5): 1020-1035.
[2]	Hui LU, Fangli ZHANG, Lei HUANG. Establishment of iBioFoundry for synthetic biology applications [J]. Synthetic Biology Journal, 2023, 4(5): 877-891.
[3]	Zhonghu BAI, He REN, Jianqi NIE, Yang SUN. The recent progresses and applications of in-parallel fermentation technology [J]. Synthetic Biology Journal, 2023, 4(5): 904-915.
[4]	Yujie WU, Xinxin LIU, Jianhui LIU, Kaiguang Yang, Zhigang SUI, Lihua ZHANG, Yukui ZHANG. Research progress of strain screening and quantitative analysis of key molecules based on high-throughput liquid chromatography and mass spectrometry [J]. Synthetic Biology Journal, 2023, 4(5): 1000-1019.
[5]	Zhehui HU, Juan XU, Guangkai BIAN. Application of automated high-throughput technology in natural product biosynthesis [J]. Synthetic Biology Journal, 2023, 4(5): 932-946.
[6]	Huan LIU, Qiu CUI. Advances and applications of ambient ionization mass spectrometry in screening of microbial strains [J]. Synthetic Biology Journal, 2023, 4(5): 980-999.
[7]	Yannan WANG, Yuhui SUN. Base editing technology and its application in microbial synthetic biology [J]. Synthetic Biology Journal, 2023, 4(4): 720-737.
[8]	Wanqiu LIU, Xiangyang JI, Huiling XU, Yicong LU, Jian LI. Cell-free protein synthesis system enables rapid and efficient biosynthesis of restriction endonucleases [J]. Synthetic Biology Journal, 2023, 4(4): 840-851.
[9]	Meili SUN, Kaifeng WANG, Ran LU, Xiaojun JI. Rewiring and application of Yarrowia lipolytica chassis cell [J]. Synthetic Biology Journal, 2023, 4(4): 779-807.
[10]	Zhi SUN, Ning YANG, Chunbo LOU, Chao TANG, Xiaojing YANG. Rational design for functional topology and its applications in synthetic biology [J]. Synthetic Biology Journal, 2023, 4(3): 444-463.
[11]	Qilong LAI, Shuai YAO, Yuguo ZHA, Hong BAI, Kang NING. Microbiome-based biosynthetic gene cluster data mining techniques and application potentials [J]. Synthetic Biology Journal, 2023, 4(3): 611-627.
[12]	Qiaozhen MENG, Fei GUO. Applications of foldability in intelligent enzyme engineering and design: take AlphaFold2 for example [J]. Synthetic Biology Journal, 2023, 4(3): 571-589.
[13]	Sheng WANG, Zechen WANG, Weihua CHEN, Ke CHEN, Xiangda PENG, Fafen OU, Liangzhen ZHENG, Jinyuan SUN, Tao SHEN, Guoping ZHAO. Design of synthetic biology components based on artificial intelligence and computational biology [J]. Synthetic Biology Journal, 2023, 4(3): 422-443.
[14]	Hailong LV, Jian WANG, Hao LV, Jin WANG, Yong XU, Dayong GU. Synthetic biology for next-generation genetic diagnostics [J]. Synthetic Biology Journal, 2023, 4(2): 318-332.
[15]	Zhaoling SHEN, Yanling WU, Tianlei YING. Synthetic biology and viral vaccine development [J]. Synthetic Biology Journal, 2023, 4(2): 333-346.