In brief

The researchers' new biosynthetic system yielded bacteria able to produce more carotenoids than natural sources.

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Bacteria turn nature’s rainbow into therapeutics

25 Jul 2022

A new bacterial platform makes plant-derived pigments more soluble, overcoming long-standing issues around their use in pharmaceuticals.

“Eat the rainbow”—a reminder to consume a diverse array of colourful fruits and vegetables to take advantage of their health-boosting pigments. Carotenoids, for example, give carrots their vivid orange colour and are also powerful antioxidants, properties that make them highly sought after for use in pharmaceuticals and beverages.

Using plant-derived pigments for therapeutics, however, isn’t easy, says Congqiang Zhang, a Junior Principal Investigator at A*STAR’s Singapore Institute of Food and Biotechnology Innovation (SIFBI).

“For example, most carotenoids are insoluble in water, which limits their application in medicine and food where enhanced water dispensability is required to facilitate their effective uptake or use,” explained Zhang.

Zhang and colleagues hypothesised a potential solution to this problem: leveraging a natural reaction used by plants and bacteria called glycosylation. Here, carbohydrate molecules such as glucose are attached to carotenoids, turning them into water-soluble compounds called carotenoid glycosides.

The researchers had previously developed an E. coli-based platform for testing the feasibility of using bacteria to create easy-to-dissolve carotenoids1. According to Zhang, the benefit of their biosynthetic system is that the microorganisms produce 1000-times more carotenoids than other natural sources such as plants. Moreover, bacterial growth conditions can be altered quickly and easily to optimise yields.

In their latest study2, the researchers expanded the capabilities of their platform to produce two additional glucosides, zeaxanthin and astaxanthin glucoside. This involved genetically engineering and controlling over 15 genes encoding enzymes from bacteria and yeasts.

Carotenoids can be glycosylated to enhance properties such as water solubility, bioavailability, photostability and biological activity for use in multiple applications.

© A*STAR Research

Balancing glucose levels, which act both as a reaction reagent and source of carbon, also proved to be important. “In addition to elegantly optimising carbon fluxes among different biosynthetic pathways, we had to identify the optimal culture conditions and carbon sources to maximise the yields of zeaxanthin glucosides and astaxanthin glucosides,” Zhang noted.

The team’s hard work paid off, with their fully optimised platform producing a promising maximum zeaxanthin glucoside yield of 78%. This work demonstrates how bacteria could overtake plants as commercial glycoside ‘biofactories’.

Giving the example of the zero-calorie sweetener stevia as an example, Zhang said: “Many glycosylated metabolites are produced in plants but they yield very low quantities and often have many unwanted isomers.”

By using synthetic biology to enhance natural reactions, the researchers have successfully created an innovative, patent-pending technique for producing glycosylated carotenoids. The team is now working on improving yields by modifying the bacteria to reduce cost, enhance stability in large bioreactors, and prime the system for large-scale industrial production.

The A*STAR-affiliated researchers contributing to this research are from the Singapore Institute of Food and Biotechnology Innovation (SIFBI).

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1. Zhang, C., Seow, V.Y., Chen, X., Too, H-P. Multidimensional heuristic process for high-yield production of astaxanthin and fragrance molecules in Escherichia coli. Nature Communications 9, 1858 (2018). | article
2. Chen, X., Lim, X., Bouin, A, Lautier, T., Zhang, C. High-level de novo biosynthesis of glycosylated zeaxanthin and astaxanthin in Escherichia coli. Bioresources and Bioprocessing 8, 67 (2021). | article

About the Researcher

Congqiang Zhang (Simon) is a Principal Investigator at the Singapore Institute of Food and Biotechnology Innovation (SIFBI). He leads a team dedicated to several academic and industrial projects. He acquired his early academic foundation in Chemical Engineering with both undergraduate and master's degrees from Tianjin University in China; later, he pursued his doctoral training in Chemical and Pharmaceutical Engineering as part of a joint programme between the National University of Singapore and the Massachusetts Institute of Technology. Zhang's area of expertise encompasses metabolic engineering, synthetic biology, enzyme engineering and the discovery and biosynthesis of natural products, which are instrumental in the field of industrial biotechnology. His scholarly contributions include co-authoring over 30 research publications and securing 10 international patents. Zhang also serves as an Associate Editor for the journals Advanced Biotechnology and Frontiers in Bioengineering and Biotechnology; he holds the position of Secretary for the BioEnergy Society of Singapore.

This article was made for A*STAR Research by Wildtype Media Group