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Progress in terpene synthesis strategies through engineering of Saccharomyces cerevisiae.

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Relation http://ir.cftri.com/13294/
http://dx.doi.org/10.1080/07388551.2017.1299679
 
Title Progress in terpene synthesis strategies through engineering of
Saccharomyces cerevisiae.
 
Creator Kalaivani, P.
Sarma, Mutturi
 
Subject 33 Terpenoids Chemistry
04 Microbiology
 
Description Terpenes are natural products with a remarkable diversity in their chemical structures and they
hold a significant market share commercially owing to their distinct applications. These potential
molecules are usually derived from terrestrial plants, marine and microbial sources. In vitro production
of terpenes using plant tissue culture and plant metabolic engineering, although receiving
some success, the complexity in downstream processing because of the interference of
phenolics and product commercialization due to regulations that are significant concerns.
Industrial workhorses’ viz., Escherichia coli and Saccharomyces cerevisiae have become microorganisms
to produce non-native terpenes in order to address critical issues such as demand-supply
imbalance, sustainability and commercial viability. S. cerevisiae enjoys several advantages for synthesizing
non-native terpenes with the most significant being the compatibility for expressing
cytochrome P450 enzymes from plant origin. Moreover, achievement of high titers such as 40 g/l
of amorphadiene, a sesquiterpene, boosts commercial interest and encourages the researchers to
envisage both molecular and process strategies for developing yeast cell factories to produce
these compounds. This review contains a brief consideration of existing strategies to engineer S.
cerevisiae toward the synthesis of terpene molecules. Some of the common targets for synthesis
of terpenes in S. cerevisiae are as follows: overexpression of tHMG1, ERG20, upc2-1 in case of all
classes of terpenes; repression of ERG9 by replacement of the native promoter with a repressive
methionine promoter in case of mono-, di- and sesquiterpenes; overexpression of BTS1 in case of
di- and tetraterpenes. Site-directed mutagenesis such as Upc2p (G888A) in case of all classes of
terpenes, ERG20p (K197G) in case of monoterpenes, HMG2p (K6R) in case of mono-, di- and sesquiterpenes
could be some generic targets. Efforts are made to consolidate various studies
(including patents) on this subject to understand the similarities, to identify novel strategies and
to contemplate potential possibilities to build a robust yeast cell factory for terpene or terpenoid
production. Emphasis is not restricted to metabolic engineering strategies pertaining to sterol
and mevalonate pathway, but also other holistic approaches for elsewhere exploitation in the S.
cerevisiae genome are discussed. This review also focuses on process considerations and challenges
during the mass production of these potential compounds from the engineered strain for
commercial exploitation.
 
Date 2017
 
Type Article
PeerReviewed
 
Format pdf
 
Language en
 
Identifier http://ir.cftri.com/13294/1/Critical%20Reviews%20in%20Biotechnology%202017.pdf
Kalaivani, P. and Sarma, Mutturi (2017) Progress in terpene synthesis strategies through engineering of Saccharomyces cerevisiae. Critical Reviews in Biotechnology, 37 (8). pp. 974-989. ISSN 0738-8551