Biorhizome: A Biosynthetic Platform for Colchicine Biomanufacturing

Abstract

Colchicine is one of the oldest plant-based medicines used to treat gout and one of the most important alkaloid-based antimitotic drugs with anticancer potential, which is commercially extracted from Gloriosa superba. Clinical trials suggest that colchicine medication could prevent atrial fibrillation recurrence after cardiac surgery. In addition, therapeutic colchicine is undergoing clinical trials to treat non-diabetic metabolic syndrome and diabetic nephropathy. However, the industrial-scale biomanufacturing of colchicine have not yet been established. Clearly, further studies on detailed biorhizome-specific transcriptome analysis, gene expression, and candidate gene validation are required before uncover the mechanism of colchicine biosynthesis and biorhizome-based colchicine biomanufacturing. Annotation of 32312 assembled multiple-tissues transcripts of G. superba represented 15088 unigenes in known plant specific gene ontology. This could help understanding colchicine biosynthesis in G. superba. This review highlights the biorhizomes, rhizome specific genes or gene what expressed with high level in rhizomes, and deep fluid dynamics in a bioreactor specifically for the biomanufacture of colchicine.

Keywords: Gloriosa superba; anticancer; antigout; bioprocess; transcriptome.

FIGURE 1

Illustration of workflow for Gloriosa superba biorhizome biomanufacturing. (A) Biorhizome induction from callus (50 ml flask) – the chemical structure is colchicine; (B) Biorhizome scaled-up in a 5 L airlift bioreactor (height: 16 inches; diameter 8 inches); (C) Harvested biorhizome from bioreactors.

FIGURE 2

Gloriosa superba gene ontology classification of assembled unigenes.

FIGURE 3

Multiphase flow mixing pattern in BTBR: (a,b) snapshots of air injection rates of 50 and 550 cc/min respectively within a 4-L working volume (water seeded with Polyamide Seeding Particles). The arrows indicate the direction of the ascending air bubbles (a,b). (c,d) Corresponding Particle Image Velocimetry to (a,b), respectively. The arrows represent the velocity field while the contours show the local vorticity intensity (c,d).