Functional Approaches to Discover New Compounds via Enzymatic Modification: Predicted Data Mining Approach and Biotransformation-Guided Purification

Abstract

In the field of biotechnology, natural compounds isolated from medicinal plants are highly valued; however, their discovery, purification, biofunctional characterization, and biochemical validation have historically involved time-consuming and laborious processes. Two innovative approaches have emerged to more efficiently discover new bioactive substances: the predicted data mining approach (PDMA) and biotransformation-guided purification (BGP). The PDMA is a computational method that predicts biotransformation potential, identifying potential substrates for specific enzymes from numerous candidate compounds to generate new compounds. BGP combines enzymatic biotransformation with traditional purification techniques to directly identify and isolate biotransformed products from crude extract fractions. This review examines recent research employing BGP or the PDMA for novel compound discovery. This research demonstrates that both approaches effectively allow for the discovery of novel bioactive molecules from natural sources, the enhancement of the bioactivity and solubility of existing compounds, and the development of alternatives to traditional methods. These findings highlight the potential of integrating traditional medicinal knowledge with modern enzymatic and computational tools to advance drug discovery and development.

Keywords: biotransformation; enzymatic synthesis; flavonoids; glycoside hydrolase; glycosylation; glycosyltransferase; phenolic compounds; predicted data mining; triterpenoids.

Figure 1

Two novel functional approaches—the PDMA and BGP—for the discovery of new and/or bioactive compounds from either commercial chemicals (the PDMA) or plant extracts (BGP).

Figure 2

Flowchart of the predicted data mining approach (PDMA).

Figure 3

Enzymatic synthesis of new catecholic compounds from loureirin A/B or isoxsuprine by BmTYR, determined through the PDMA [8,9].

Figure 4

Enzymatic synthesis of new glucosides from corylin or skullcapflavone II by BsUGT489, determined through the PDMA. UDP-G: uridine diphosphate glucose. UDP: uridine diphosphate.

Figure 5

Enzymatic synthesis of new methyl compounds from plantagoside by SpOMt2884, determined through the PDMA. SAM: S-adenosylmethionine. SAH: S-adenosylhomocysteine.

Figure 6

Biotransformation-guided purification (BGP) workflow.

Figure 7

Enzymatic synthesis of a new glucoside from Ganoderma lucidum by BsUGT489 through BGP [12].

Figure 8

Enzymatic synthesis of a new glucoside from Baizhi herb by DgAS through BGP.

Figure 9

Enzymatic synthesis of new catecholic compounds from licorice or Ha-Soo-Oh by BmTYR through BGP [14,15].