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Last update 08 May 2025

Sun Pharmaceutical Industries (Australia) Pty Ltd.

Subsidiary Company|Australia|

www.sunpharma.com

Subsidiary Company|Australia|

www.sunpharma.com

Last update 08 May 2025

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Translational Medicine

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100 Clinical Results associated with Sun Pharmaceutical Industries (Australia) Pty Ltd.

0 Patents (Medical) associated with Sun Pharmaceutical Industries (Australia) Pty Ltd.

Literatures (Medical) associated with Sun Pharmaceutical Industries (Australia) Pty Ltd.

20 Sep 2024·Organic Process Research & Development

Optimized Enzyme Production for the Escherichia coli Whole-Cell Biocatalytic Synthesis of Codeine from Thebaine

Author: Mutch, George ; Luna-Flores, Carlos Horacio ; Stevens, Geoffrey W. ; Velasquez Agudelo, Andres ; Speight, Robert E. ; Gras, Sally L. ; Li, Xu ; Jahanian, Ali ; Fry, Fiona

Codeine, the most widely used medicinal opiate in the world, can be produced from thebaine by using an environmentally friendly biocatalytic process using purified enzymes or microbial cells.However, this biotransformation is either inefficient or not systematically characterized for industrial use, as microbial fermentation and enzyme expression have not been optimized, and the production of the undesirable side product neopine reduces yields.In this study, the expression of the required enzymes in a reengineered Escherichia coli system was optimized using a two-step design of experiments approach.Higher yields of biomass and enzyme expression were achieved in a defined minimal medium using lactose for induction.The interaction between temperature and lactose concentration was optimized, leading to an improvement in the apparent volumetric activity of thebaine 6-O-demethylase (T6ODM) from 45 to 776 U·L^-1 using glycerol as the carbon source and an improvement in the apparent volumetric activity of codeinone reductase (COR) from 120 to 3707 U·L^-1 using glucose.The productivity for T6ODM and COR was also increased 4.5 and 5.7-times to 8.0 and 28.3 U·L^-1·h^-1, resp., in fed-batch cultivations compared to in shake flasks.With the optimized conditions for enzyme expression, the whole-cell biotransformation led to an 80% yield of codeine from thebaine and a final codeine/neopine molar ratio of 85:15.The inclusion of coexpressed neopinone isomerase, which catalyzes the production of codeinone from neopinone, reduced neopine production at the start of the reaction when the concentration of neopinone was low but did not improve the final codeine/neopine ratio as the reaction progressed and the concentration of neopinone increased.This observation may provide a further understanding of the differences between catalytic conditions in a bioreactor and the poppy plant, where the concentration of pathway intermediates such as neopinone is likely to be low and no neopine is observedOverall, the process improvements reported here provide progress toward an industrial biocatalytic production of codeine from thebaine.

01 May 2017·TalantaQ2 · CHEMISTRY

Application of 2D-HPLC coupled with principal component analysis to study an industrial opiate processing stream

Q2 · CHEMISTRY

Article

Author: Francis, Paul S ; Purcell, Stuart D ; Conlan, Xavier A ; Barnett, Neil W ; Stevenson, Paul G ; Burns, Niki K ; Fry, Fiona

Principal component analysis (PCA) loading plots were used to elucidate key differences between two-dimensional high performance liquid chromatography (2D-HPLC) fingerprint data from samples collected from stages along the Papaver somniferum industrial process chemistry workflow. Data reduction was completed using a 2D-HPLC peak picking approach as a precursor to chemometric analysis. Using comparisons of the final stages of product extraction as an example, PCA analysis of characteristic 2D-HPLC fingerprints accounted for 84.9% of variation between the two sample sets measured in triplicate, with 64.7% explained by PC1. Loadings plots of PC1 on each sample set identified where the significant changes were occurring and normalised bubble plots provided an indication of the relative importance of each of these changes. These findings highlight 2D-HPLC with appropriate chemometric analysis as a useful tool for the exploration of bioactive molecules within biomass.

Chemical Communications

An industrially applicable Escherichia coli platform for bioconversion of thebaine to oripavine and codeine to morphine

Article

Author: Gras, Sally L ; Spencer, Garrick W K ; Li, Xu ; Jarrold, Ailsa

A whole cell Escherichia coli biotransformation platform converting thebaine to oripavine and codeine to morphine was demonstrated with industrially applicable yields (∼1.2 × 10−2 g L−1 h−1 or ∼1.2 × 10−1 g L−1 h−1), improving >13 400-fold upon morphine production in yeast.

100 Deals associated with Sun Pharmaceutical Industries (Australia) Pty Ltd.

100 Translational Medicine associated with Sun Pharmaceutical Industries (Australia) Pty Ltd.

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Sun Pharmaceutical Industries (Australia) Pty Ltd.

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