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Identification of RoCYP01 (CYP716A155) enables construction of engineered yeast for high-yield production of betulinic acid
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Identification of RoCYP01 (CYP716A155) enables construction of engineered yeast for high-yield production of betulinic acid
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Journal Article
Identification of RoCYP01 (CYP716A155) enables construction of engineered yeast for high-yield production of betulinic acid
2019
Overview
Betulinic acid (BA) and its derivatives possess potent pharmacological activity against cancer and HIV. As with many phytochemicals, access to BA is limited by the requirement for laborious extraction from plant biomass where it is found in low amounts. This might be alleviated by metabolically engineering production of BA into an industrially relevant microbe such as
Saccharomyces cerevisiae
(yeast), which requires complete elucidation of the corresponding biosynthetic pathway. However, while cytochrome P450 enzymes (CYPs) that can oxidize lupeol into BA have been previously identified from the CYP716A subfamily, these generally do not seem to be specific to such biosynthesis and, in any case, have not been shown to enable high-yielding metabolic engineering. Here RoCYP01 (CYP716A155) was identified from the BA-producing plant
Rosmarinus officinalis
(rosemary) and demonstrated to effectively convert lupeol into BA, with strong correlation of its expression and BA accumulation. This was further utilized to construct a yeast strain that yields > 1 g/L of BA, providing a viable route for biotechnological production of this valuable triterpenoid.
Publisher
Springer Berlin Heidelberg,Springer,Springer Nature B.V
Subject
/ Biomedical and Life Sciences
/ Biotechnological Products and Process Engineering
/ Cytochrome P-450 Enzyme System - classification
/ Cytochrome P-450 Enzyme System - genetics
/ Cytochrome P-450 Enzyme System - metabolism
/ Enzymes
/ genetically engineered microorganisms
/ HIV
/ Human immunodeficiency virus
/ lupeol
/ Microbial Genetics and Genomics
/ Pentacyclic Triterpenes - metabolism
/ Recombinant Proteins - genetics
/ Recombinant Proteins - metabolism
/ Rosemary
/ Saccharomyces cerevisiae - enzymology
/ Saccharomyces cerevisiae - genetics
/ Saccharomyces cerevisiae - metabolism
/ Saccharomyces cerevisiae Proteins - genetics
/ Saccharomyces cerevisiae Proteins - metabolism
/ Yeast
/ yeasts
