Abstract
With the successful production of artemisinic acid in yeast, the promising potential of synthetic biology for natural product biosynthesis is now being realized. The recent total biosynthesis of opioids in microbes is considered to be another landmark in this field. The importance and significance of enzymes in natural product biosynthetic pathways have been re-emphasized by these advancements. Therefore, the characterization and elucidation of enzymatic function in natural product biosynthesis are undoubtedly fundamental for the development of new drugs and the heterologous biosynthesis of active natural products. Here, discoveries regarding enzymatic function in natural product biosynthesis over the past year are briefly reviewed.
Highlights
In 2013, artemisinic acid, a pharmaceutical precursor of artemisinin, which is a potent antimalarial drug produced by the sweet wormwood plant Artemisia annua[3], was first produced in an engineered Saccharomyces cerevisiae strain[4]
Well-known opioids have been successfully biosynthesized in S. cerevisiae[7]; this is considered to be the most complicated and elaborate engineering work ever achieved in the field, and it is a remarkable landmark in the increasingly sophisticated use of synthetic biology to engineer complex metabolic pathways into microbes[8]
The success of microbial total biosynthesis of opioids reveals the significant functions of enzymes in recent drug development applications, as well as in the field of synthetic biology
Summary
Identification of the enzymes DRS and DRR remove the last stumbling block in the complete synthesis of opioids The secondary metabolites of higher plants include diverse chemicals, such as isoprenoids, phenolic compounds, and alkaloids Among these natural products, alkaloids are very important medicines. Hawkins and Smolke reported that by feeding chemically synthesized (R,S)-norlaudanosoline as a starting substrate, (R,S)-reticuline could be produced in engineered yeast, and that by using the human P450 enzyme CYP2D6 in this pathway, (R)-reticuline can be converted to the morphinan alkaloid salutaridine[16] As noted in these studies, the starting substrates dopamine and (R, S)-norlaudanosoline are intermediate products in the BIA metabolic pathway. The success of microbial total biosynthesis of opioids reveals the significant functions of enzymes in recent drug development applications, as well as in the field of synthetic biology. I confirm that the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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