Compartmentalization and transporter engineering strategies for terpenoid synthesis

Abstract

Microbial cell factories for terpenoid synthesis form a less expensive and more environment-friendly approach than chemical synthesis and extraction, and are thus being regarded as mainstream research recently. Organelle compartmentalization for terpenoid synthesis has received much attention from researchers owing to the diverse physiochemical characteristics of organelles. In this review, we first systematically summarized various compartmentalization strategies utilized in terpenoid production, mainly plant terpenoids, which can provide catalytic reactions with sufficient intermediates and a suitable environment, while bypassing competing metabolic pathways. In addition, because of the limited storage capacity of cells, strategies used for the expansion of specific organelle membranes were discussed. Next, transporter engineering strategies to overcome the cytotoxic effects of terpenoid accumulation were analyzed. Finally, we discussed the future perspectives of compartmentalization and transporter engineering strategies, with the hope of providing theoretical guidance for designing and constructing cell factories for the purpose of terpenoid production.

Enhancing Trans-Nerolidol Productivity in Yarrowia lipolytica by Improving Precursor Supply and Optimizing Nerolidol Synthase Activity

“…To circumvent nonproductive consumption of intermediates and reduce cell toxicity caused by excessive metabolites, compartmentalizing is usually a good solution for heterologous biosynthesis. , The peroxisome is considered to have a high content of the acetyl-CoA pool from the β-oxidation of fatty acids, rendering it more propitious for MVA pathway compartmentalization . Here, the enhanced peroxisome targeting sequence (ePTS1) was employed to target enzymes of the trans -nerolidol biosynthetic pathway into the peroxisome.…”

SynBio 2.0, a new era for synthetic life: Neglected essential functions for resilience

“…The solution is to implement compartmentalization, omnipresent in existing living organisms (de Lorenzo et al, 2015; Quinlivan et al, 2003). From this perspective, organelle compartmentalization for terpenoid synthesis has been the subject of much research attention, due to the diversity of the original physico‐chemical characteristics of organelles (Jin et al, 2022). A rather different, but certainly effective, way of compartmentalizing metabolic reactions is to set up co‐cultures involving different organisms that develop sub‐pathways assembled together via their import and export of intermediates.…”

Compartmentalization engineering of yeasts to overcome precursor limitations and cytotoxicity in terpenoid production

“…Frontiers in Bioengineering and Biotechnology frontiersin.org Yocum et al, 2021;Jin et al, 2022), as shown in Table 1. The physiological properties of various organelles as well as their benefits and drawbacks for organelle compartmentalization in terpenoid production (Jin et al, 2022), which will not be discussed below.…”

“…Frontiers in Bioengineering and Biotechnology frontiersin.org Yocum et al, 2021;Jin et al, 2022), as shown in Table 1. The physiological properties of various organelles as well as their benefits and drawbacks for organelle compartmentalization in terpenoid production (Jin et al, 2022), which will not be discussed below. In this review, we summarize the characteristics of monoterpenoids, sesquiterpenoids and tetraterpenoids and focuse on their unique requirements for improving terpenoid production through organelle compartmentalization.…”