Toward improved terpenoids biosynthesis: strategies to enhance the capabilities of cell factories

Abstract

Terpenoids form the most diversified class of natural products, which have gained application in the pharmaceutical, food, transportation, and fine and bulk chemical industries. Extraction from naturally occurring sources does not meet industrial demands, whereas chemical synthesis is often associated with poor enantio-selectivity, harsh working conditions, and environmental pollutions. Microbial cell factories come as a suitable replacement. However, designing efficient microbial platforms for isoprenoid synthesis is often a challenging task. This has to do with the cytotoxic effects of pathway intermediates and some end products, instability of expressed pathways, as well as high enzyme promiscuity. Also, the low enzymatic activity of some terpene synthases and prenyltransferases, and the lack of an efficient throughput system to screen improved high-performing strains are bottlenecks in strain development. Metabolic engineering and synthetic biology seek to overcome these issues through the provision of effective synthetic tools. This review sought to provide an in-depth description of novel strategies for improving cell factory performance. We focused on improving transcriptional and translational efficiencies through static and dynamic regulatory elements, enzyme engineering and high-throughput screening strategies, cellular function enhancement through chromosomal integration, metabolite tolerance, and modularization of pathways. Graphical Abstract

Plants strike back: Plant volatiles and their role in indirect defence against aphids

“…Terpenoids are characterised by enormous diversity and comprise over 80,000 compounds (Christianson, 2017), at least half of which have been identified in plants (Tholl, 2015). Such diversity leads to a wide range of beneficial properties that have found commercial application in various sectors, and the demand for terpenoids has increased to such an extent that their synthetic production is a trending topic in current research (Fordjour et al, 2022). Natural biosynthesis (Figure 1) involves two independent pathways that generate the universal C5 precursors of terpenoids: the mevalonate (MVA) pathway or HMG‐CoA reductase pathway and the 2‐C‐methyl‐D‐erythritol 4‐phosphate (MEP) pathway, also known as the 1‐deoxy‐D‐xylulose 5‐phosphate (DXP) pathway.…”

“…Terpenoids are characterised by enormous diversity and comprise over 80,000 compounds (Christianson, 2017), at least half of which have been identified in plants (Tholl, 2015). Such diversity leads to a wide range of beneficial properties that have found commercial application in various sectors, and the demand for terpenoids has increased to such an extent that their synthetic production is a trending topic in current research (Fordjour et al, 2022). Natural The conventional view is that the MVA pathway in plants provides the precursors to produce sesquiterpenes in the cytosol, whereas the MEP pathway functions in the plastids (Lin & Pakrasi, 2019) and produces mainly mono-, di-and tetraterpenes.…”

Compartmentalization and transporter engineering strategies for terpenoid synthesis

“…Higher titers may still be difficult to achieve if continuous terpenoid accumulation is noted in cells because of the limited storage capacity and their toxicity to organelles, proteins, DNA, and other biological processes [ 100 , 101 ]. As a result, engineering efflux pumps to export terpenoids and thus reduce terpenoid cytotoxicity may be a promising solution [ 102 , 103 ].…”

Functional bioactive compounds in ginger, turmeric, and garlic

“…The final step involves the removal of the cyclic allylic proton and the subsequent double bond formation. The enzyme responsible for catalyzing this reaction is known as zingiberene synthase and is used in forming other mono- and sesquiterpenes ( 23 ).…”