Abstract
Monoterpenes are commonly applied as pharmaceuticals and valuable chemicals in various areas. The bioproduction of valuable monoterpenes in prokaryotic microbial hosts, such as E. coli, has progressed considerably thanks to the development of different outstanding approaches. However, the large-scale production of monoterpenes still presents considerable limitations. Thus, process development warrants further investigations. This review discusses the endogenous methylerythritol-4-phosphate-dependent pathway engineering and the exogenous mevalonate-dependent isoprenoid pathway introduction, as well as the accompanied optimization of rate-limiting enzymes, metabolic flux, and product toxicity tolerance. We suggest further studies to focus on the development of systematical, integrational, and synthetic biological strategies in light of the inter disciplines at the cutting edge. Our review provides insights into the current advances of monoterpene bioengineering and serves as a reference for future studies to promote the industrial production of valuable monoterpenes.
Highlights
Terpenoids are widely distributed natural compounds that are extracted from plants, algae, mosses, and even insects and microbes
isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) are subsequently transformed to geranyl pyrophosphate (GPP), farnesyl pyrophosphate (FPP), or geranylgeranyl pyrophosphate (GGPP), which are the precursors of monoterpenes, sesquiterpenes, and diterpenes, respectively [7]
Two major pathways are involved in the natural synthesis of isoprenoid precursors IPP and DMAPP: the methylerythritol-4-phosphate-dependent pathway (MEP pathway), termed as deoxyxylulose phosphate pathway (DXP pathway) and the mevalonate-dependent isoprenoid pathway (MEV pathway) [8,9]
Summary
Terpenoids are widely distributed natural compounds that are extracted from plants, algae, mosses, and even insects and microbes. Such modes of production could hardly synthesize compounds with complex molecular structure and specific affinity and specificity [24] To address these problems and achieve broad commercial applications, scholars have developed a series of biological manufacturing methods with the advantages of self-assembly, proliferation, mild reaction condition requirements, and environment-friendly features to produce valuable monoterpenes, especially in this rapid development era of synthetic biology and bioengineering [25,26]. Several microorganisms, such as Escherichia coli and Saccharomyces cerevisiae, are considered as perfect chassis and have been designed as microbial cell factories for the industrialized production of significant monoterpenoids [27,28]. This review summarizes the advances of different strategies for the establishment and optimization of heterologous monoterpene synthesis in the prokaryotic cell factory (Table 1)
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