미생물을 이용한 L-트립토판 유래 방향족 화합물 생산 최근 연구

국문 초록 (Abstract)

방향족 화합물은 화학, 식품, 고분자, 화장품, 의약 산업 등에 이용되는 중요한 물질로, 현재까지 대부분 화학합성법 또는 식물 추출법으로 만들어진다. 그러나, 화석 연료의 고갈, 지구 온난화, 환경규제의 강화, 식물자원의 과다한 채취 등의 많은 위협요인에 직면하면서 재생 가능한 생물자원을 이용한 미생물을 이용한 생물공학적 방법으로 방향족 화합물을 생산하는 것은 매우 유망한 대안이다. 대사공학이 합성생물학과 접목되면서, L-트립토판 생합성 경로 유래의 인공 생합성 경로가 재 구축되어 5-히드록시트립토판, 세로토닌, 멜라토닌, 7-염화-L-트립토판, 7-브로모-L-트립토판, 인디고, 인디루빈, 인돌-3-초산, 바이오라세인, 데옥시바이오라세인과 같은 다양한 고부가 화합물을 생산할 수 있게 되었다. 본 총설은 이러한 방향족 화합물의 특성, 용도, 생합성 경로를 요약하였다. 또한 방향족 화합물을 미생물을 이용하여 생산하기 위한 최신의 대사공학 전략과 생산 농도를 올리는데 제기되는 문제들을 극복하기 위한 해결방안 등을 정리하여 보고한다. 시스템 대사 공학에 기반한 균주 개발과 재생 가능한 생물자원을 사용한 배지 및 생물공정의 최적화가 이루어지면 방향족 화합물의 미생물 생산을 위한 상업적으로 실행 가능한 기술 개발을 가능하게 할 것으로 예상된다.

다국어 초록 (Multilingual Abstract)

Aromatic compounds are widely used in the chemical, food, polymer, cosmetic, and pharmaceutical industries and are produced by mainly chemical synthesis using benzene, toluene, and xylene or by plant extraction methods. Due to many rising threats, including the depletion of fossil fuels, global warming, the strengthening of international environmental regulations, and the excessive harvesting of plant resources, the microbial production of aromatic compounds using renewable biomass is regarded as a promising alternative. By integrating metabolic engineering with synthetic and systems biology, artificial biosynthetic pathways have been reconstituted from L-tryptophan biosynthetic pathway in relevant microorganisms, such as Escherichia coli and Corynebacterium glutamicum, enabling the production of a variety of value-added aromatic compounds, such as 5-hydroxytryptophan, serotonin, melatonin, 7-chloro-L-tryptophan, 7-bromo-L-tryptophan, indigo, indirubin, indole-3-acetic acid, violacein, and dexoyviolacein. In this review, we summarize the characteristics, usage, and biosynthetic pathways of these aromatic compounds and highlight the latest metabolic engineering strategies for the microbial production of aromatic compounds and suitable solution strategies to overcome problems in increasing production titers. It is expected that strain development based on systems metabolic engineering and the optimization of media and bioprocesses using renewable biomass will enable the development of commercially viable technologies for the microbial production of many aromatic compounds.

목차 (Table of Contents)

• 서론
• 본론
• 결론
• References
• 초록

참고문헌 (Reference)

1 이진호, "화이트바이오텍기반 방향족화합물 개발에 관한 연구동향" 한국미생물·생명공학회 37 (37): 306-315, 2009

2 Koguchi, Y., "TMC-94A, B, C, and D, novel proteasome inhibitors produced by Apiospora montagnei Sacc. TC 1093. Taxonomy, production, isolation, and biological activities" 53 : 105-109, 2000

3 Rodrigues, A. L., "Systems metabolic engineering of Escherichia coli for production of the antitumor drugs violacein and deoxyviolacein" 20 : 29-41, 2013

4 Mora-Villalobos, J. A., "Synthetic pathway and processes for effective production of 5-hydroxytryptophan and serotonin from glucose in Escherichia coli" 12 : 3-, 2018

5 van Pée, K. H., "Specific enzymatic chlorination of tryptophan and tryptophan derivatives" 467 : 603-609, 1999

6 Zhou, N. Y., "Salicylate 5-hydroxylase from Ralstonia sp. strain U2: a monooxygenase with close relationships to and shared electron transport proteins with naphthalene dioxygenase" 184 : 1547-1555, 2002

7 강미숙, "Rhodococcus sp. RHA1 유래의 Indole Oxygenase의 클로닝 및 발현" 한국미생물·생명공학회 37 (37): 197-203, 2009

8 Chen, Y., "Rational design and analysis of an Escherichia coli strain for high-efficiency tryptophan production" 45 : 357-367, 2018

9 정혜숙, "Protein Engineering of Flavin-containing Monooxygenase from Corynebacterium glutamicum for Improved Production of Indigo and Indirubin" 한국생명과학회 28 (28): 656-662, 2018

10 Lee, J. H., "Production of amino acids-Genetic and metabolic engineering approaches" 245 : 1575-1587, 2017

11 김유미, "Production of Indole-3-acetate in Corynebacterium glutamicum by Heterologous Expression of the Indole-3-pyruvate Pathway Genes" 한국미생물·생명공학회 47 (47): 242-249, 2019

12 Eisenbrand, G., "Molecular mechanisms of indirubin and its derivatives : novel anticancer molecules with their origin in traditional Chinese phytomedicine" 130 : 627-635, 2004

13 Nishizawa, T., "Molecular analysis of the rebeccamycin L-amino acid oxidase from Lechevalieria aerocolonigenes ATCC 39243" 187 : 2084-2092, 2005

14 Pawar, S., "Microbial pyrrolnitrin : Natural metabolite with immense practical utility" 9 : 443-, 2019

15 Wang, H., "Metabolic pathway engineering for high-level production of 5-hydroxytryptophan in Escherichia coli" 48 : 279-287, 2018

16 Huccetogullari, D., "Metabolic engineering of microorganisms for production of aromatic compounds" 18 : 41-, 2019

17 Du, J., "Metabolic engineering of Escherichia coli for the production of indirubin from glucose" 267 : 19-28, 2018

18 Veldmann, K. H., "Metabolic engineering of Corynebacterium glutamicum for the fermentative production of halogenated tryptophan" 291 : 7-16, 2019

19 Byeon, Y., "Melatonin production in Escherichia coli by dual expression of serotonin N-acetyltransferase and caffeic acid O-methyltransferase" 100 : 6683-6691, 2016

20 Arnao, M. B., "Melatonin and its relationship to plant hormones" 121 : 195-207, 2018

21 Spaepen, S., "Indole-3-acetic acid in microbial and microorganism-plant signaling" 31 : 425-448, 2007

22 Hammer, P. E., "Four genes from Pseudomonas fluorescens that encode the biosynthesis of pyrrolnitrin" 63 : 2147-2154, 1997

23 McKinney, J., "Expression and purification of human tryptophan hydroxylase from Escherichia coli and Pichia pastoris" 33 : 185-194, 2004

24 Zhou, Y., "Enhanced production of crude violacein from glucose in Escherichia coli by overexpression of rate-limiting key enzyme(s)involved in violacein biosynthesis" 186 : 909-916, 2018

25 Han, G. H., "Enhanced indirubin production in recombinant Escherichia coli harboring a flavin-containing monooxygenase gene by cysteine supplementation" 164 : 179-187, 2012

26 Lin, Y., "Engineering bacterial phenylalanine 4-hydroxylase for microbial synthesis of human neurotransmitter precursor 5-hydroxytryptophan" 3 : 497-505, 2014

27 Sun, H., "Engineering Corynebacterium glutamicum for violacein hyper production" 15 : 148-, 2016

28 Hsu, T. M., "Employing a biochemical protecting group for a sustainable indigo dyeing strategy" 14 : 256-261, 2018

29 Kim, J., "Eluciding cysteine-assisted synthesis of indirubin by a flavin-containing monooxygenase" 9 : 9539-9544, 2019

30 Elisa Friska Romasi, "Development of Indole-3-Acetic Acid-Producing Escherichia coli by Functional Expression of IpdC, AspC, and Iad1" 한국미생물·생명공학회 23 (23): 1726-1736, 2013

31 Guo, D., "De novo biosynthesis of indole-3-acetic acid in engineered Escherichia coli" 67 : 8186-8190, 2019

32 Ikeda, M., "Corynebacterium glutamicum" Springer 175-226, 2020

33 Kubota, T., "Chorismate-dependent transcriptional regulation of quinate/shikimate utilization genes by LysR-type transcriptional regulator QsuR in Corynebacterium glutamicum : carbon flow control at metabolic branch point" 92 : 356-368, 2014

34 Ameria, S. P. L., "Characterization of a flavin-containing monooxygenase from Corynebacterium glutamicum and its application to production of indigo and indirubin" 37 : 1637-1644, 2015

35 Du, L., "Central metabolic pathway modification to improve L-tryptophan production in Escherichia coli" 10 : 59-70, 2019

36 Cao, M., "Building microbial factories for the production of aromatic amino acid pathway derivatives : From commodity chemicals to plant-sourced natural products" 58 : 94-132, 2020

37 Veldmann, K. H., "Bromination of L-tryptophan in a fermentative process with Corynebacterium glutamicum" 7 : 219-, 2019

38 Lee, J. H., "Biotechnological production of aromatic compounds of the extended shikimate pathway from renewable biomass" 257 : 211-221, 2017

39 Spaepen, S., "Auxin and plant-microbe interactions" 3 : a001438-, 2011

40 Choi, H. S., "A novel flavin-containing monooxygenase from Methylophaga sp. strain SK1 and its indigo synthesis in Escherichia coli" 306 : 930-936, 2003