Fig. 8 Structures of Corosolic Acid and Ursolic Acid
28-O-Β-D-Glucopyranoside
Glycosylation involves the attachment of one or more sugar moieties to
the parent compound and contributes for diverse physicochemical
properties, such as water solubility, structural integrity and
pharmacological efficacy 80. To achieve the
glycosylated derivatives, heterologous expression of
UDP-glycosyltransferases (UGTs) is less frequent due to their lower in
vivo catalytic activity. In relation to glycyrrhetinic acid, structural
diversification of UA by glycosylation is still in infancy. In one
study, transcriptomic data analysis of Ilex Asprella revealed
UGT74AG5 and its expression in UA-producing S. cerevisiae strain
confirmed its glycosylation activity against UA to synthesize its
glycosylated derivative, UA-28-O-β-D-glucopyranoside102 (Fig. 8 ). Although the synthesis of UA
derivatives in cell factories is still in its infancy, the de novo
synthesis of UA in S. cerevisiae provides strong support for its
development.
Perspective
UA exhibits significant therapeutic properties to be used in disease
management and drug development. UA derivatives with different
structural modifications have been designed and synthesized to explore
more effective therapeutic products with higher oral bioavailability and
efficacy. Particularly, many structurally modified UA derivatives by
chemical means seem to be effective against variety of cancer cell lines
in vitro. Due to the great value potential and pharmacological
manifestations of UA and its derivatives, there is a need to develop an
economical and feasible approach to produce the high yield of UA and its
varied derivatives.
Although considerable efforts are currently being made to develop
effective approaches for sequestering UA from various medicinal plants,
its biosynthesis in microbial cell factories is a more attractive
strategy. In this regard, S. cerevisiae presents a potential
microbial host to synthesize terpenoids efficiently. However,
bioengineering strategies for bioproduction of either UA or its
derivatives have not been developed effectively. With the advent in
synthetic biology and metabolic engineering, improved metabolic pathways
and key enzyme-protein engineering lead to efficient biosynthesis of
valuable products, which provides strong support for better utilizingS. cerevisiae as a cell factory. Increased production of terpene
derivatives in S. cerevisiae can be achieved by optimization of
endogenous pathways, employing CRISPR gene editing technology,
modification of key enzymes and utilization of synthetic S.
cerevisiae chromosome system (SCRaMbLE). More importantly, there are
powerful tools such as computational biology, genomics and
transcriptomics accompanied by synthetic biology to identify and
manipulate novel terpenoid synthesis pathways in microbial cell
factories for their green production. Advances in synthetic biology
technology will promote to develop a fully automated robotic screening
platform for high-throughput screening of engineered strains.
Combination of different regulation strategies to design and improve the
metabolic pathways in S. cerevisiae is expected to be an
efficient approach over the traditional methods to sequester UA and its
derivatives in future for further exploration. Although there is a long
way to go to develop an economically feasible and easy method for UA,
its rich pharmacological activity and great value potential are worthy
of extensive exploration in many scientific fields.