Fermentative production and direct extraction of (-)-α-bisabolol in metabolically engineered Escherichia coli = 재조합 대장균을 이용한 비사볼올의 발효 생산 및 추출

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Title
Fermentative production and direct extraction of (-)-α-bisabolol in metabolically engineered Escherichia coli = 재조합 대장균을 이용한 비사볼올의 발효 생산 및 추출
Author(s)
Gui Hwan Han; Seong Keun Kim; Paul Kyung-Seok Yoon; Kang Young Hwan; B S Kim; Y Fu; Bong Hyun SungHeung Chae JungDae-Hee Lee; S W Kim; Seung Goo Lee
Bibliographic Citation
Microbial Cell Factories, vol. 15, pp. 185-185
Publication Year
2016
Abstract
Background: (-)-α-Bisabolol, also known as levomenol, is an unsaturated sesquiterpene alcohol that has mainly been used in pharmaceutical and cosmetic products due to its anti-inflammatory and skin-soothing properties. (-)-α-Bisabolol is currently manufactured mainly by steam-distillation of the essential oils extracted from the Brazilian candeia tree that is under threat because its natural habitat is constantly shrinking. Therefore, microbial production of (-)-α-bisabolol plays a key role in the development of its sustainable production from renewable feedstock. Results: Here, we created an Escherichia coli strain producing (-)-α-bisabolol at high titer and developed an in situ extraction method of (-)-α-bisabolol, using natural vegetable oils. We expressed a recently identified (-)-α-bisabolol synthase isolated from German chamomile (Matricaria recutita) (titer: 3mg/L), converted the acetyl-CoA to mevalonate, using the biosynthetic mevalonate pathway (12.8mg/L), and overexpressed farnesyl diphosphate synthase to efficiently supply the (-)-α-bisabolol precursor farnesyl diphosphate. Combinatorial expression of the exogenous mevalonate pathway and farnesyl diphosphate synthase enabled a dramatic increase in (-)-α-bisabolol production in the shake flask culture (80mg/L) and 5L bioreactor culture (342mg/L) of engineered E. coli harboring (-)-α-bisabolol synthase. Fed-batch fermentation using a 50L fermenter was conducted after optimizing culture conditions, resulting in efficient (-)-α-bisabolol production with a titer of 9.1g/L. Moreover, a green, downstream extraction process using vegetable oils was developed for in situ extraction of (-)-α-bisabolol during fermentation and showed high yield recovery (>98%). Conclusions: The engineered E. coli strains and economically viable extraction process developed in this study will serve as promising platforms for further development of microbial production of (-)-α-bisabolol at large scale.
Keyword
(-)-α-Bisabolol(-)-α-Bisabolol synthaseEscherichia coliFarnesyl diphosphate synthaseIn situ extractionMevalonate pathwayVegetable oils
ISSN
1475-2859
Publisher
Springer-BMC
DOI
http://dx.doi.org/10.1186/s12934-016-0588-2
Type
Article
Appears in Collections:
Division of Bio Technology Innovation > SME Support Center > 1. Journal Articles
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