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. 2021 Feb 19;14(6):2497–2513. doi: 10.1111/1751-7915.13768

Table 1.

Bisabolene production in the metabolically engineered microbial hosts.

Host Product Titer Yield Productivity Strategy Reference
Y. lipolytica α‐bisabolene 973.1 mg l‐1 8.11 mg l‐1 h‐1 Producing α‐bisabolene, β‐bisabolene and γ‐bisabolene through heterologous expression of the α‐bisabolene synthase from A. grandis, the β‐bisabolene synthase gene from Z. officinale and the γ‐bisabolene synthase gene from H. annuus respectively. Subsequently, overexpression of the endogenous mevalonate pathway genes and introduction of heterologous multidrug efflux transporters. Furthermore, the fermentation conditions were optimized to maximize bisabolene production by the engineered Y. lipolytica strains from glucose In this study
β‐bisabolene 68.2 mg l‐1 0.56 mg l‐1 h‐1
γ‐bisabolene 20.2 mg l‐1 0.17 mg l‐1 h‐1
E. coli α‐bisabolene 912 mg l‐1 182.4 mg g glucose‐1 12.49 mg l‐1 h‐1 The heterologous codon‐optimized version of the highest α‐bisabolene synthase gene Ag1 from A. grandis was coexpressed with four homologous codon‐optimized genes tHMGR, HMGS, MK and PMK involved in the MVA pathway from S. cerevisiae under control of a strong promoter Ptrc (Peralta‐Yahya et al., 2011)
bisabolene 1.1 g l‐1 15.28 mg l‐1 h‐1 Inducer‐free bisabolene production was achieved by expressing LuxR/LuxI effector‐regulator proteins and using PluxI responsive promoter to drive target biosynthesis pathway with a QS system (Kim et al., 2017)
S. cerevisiae α‐bisabolene 994 mg l‐1 10.35 mg l‐1 h‐1 The heterologous codon‐optimized version of the highest α‐bisabolene synthase gene Ag1 from A. grandis was coexpressed with the truncated HMG‐CoA reductase (tHMGR), the FPP synthase (Erg20), and the global transcription regulator of the sterol pathway upc2‐1 and the squalene synthase (Erg9) was downregulated (Peralta‐Yahya et al., 2011)
bisabolene 5.2 g l‐1 250 mg g glucose‐1 217 mg l‐1 h‐1 Introducing gene deletions (YJL064W, YPL062W and ROX1) into strains. Overexpressed tHMG1 and ERG20 along with the AgBIS and downregulated ERG9 (Ӧzaydın etal., 2013)
Synechococcus sp. PCC 7002 α‐bisabolene 0.6 mg l‐1 6.25 µg l‐1 h‐1 The heterologous A. grandis α‐bisabolene synthase gene Ag1 was expressed. (Davies et al., 2014)
Synechocystis sp. PCC 6803 α‐bisabolene 22.2 mg l‐1 0.03 mg l‐1 h‐1 Improving heterologous protein expression in Synechocystis sp. PCC 6803 by combining RBS calculator and codon optimizations under light condition (Sebesta and Peebles, 2019)
Chlamydomonas reinhardtii α‐bisabolene 11 mg l‐1 0.07 mg l‐1 h‐1 Combining sequential enzyme loading and amiRNA knockdown from four separate genetic constructs and using different carbon and light regimes (Wichmann et al., 2017)
Rhodosporidium toruloides bisabolene 680 mg l‐1 5.04 mg l‐1 h‐1 Growing in corn stover hydrolysates prepared by two different pretreatment methods, one using a novel biocompatible ionic liquid (IL) choline α‐ketoglutarate at bench scale, and the other using an alkaline pretreatment in a high‐gravity fed‐batch bioreactor (Yaegashi et al., 2017)