Campus Units

Biochemistry, Biophysics and Molecular Biology, Roy J. Carver Department of

Document Type

Article

Publication Version

Accepted Manuscript

Publication Date

7-15-2019

Journal or Book Title

Applied Microbiology and Biotechnology

DOI

10.1007/s00253-019-10004-z

Abstract

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.

Comments

This is a manuscript of an article published as Huang, Jiajian, Wenlong Zha, Tianyue An, Hua Dong, Ying Huang, Dong Wang, Rongmin Yu et al. "Identification of RoCYP01 (CYP716A155) enables construction of engineered yeast for high-yield production of betulinic acid." Applied microbiology and biotechnology (2019). doi: 10.1007/s00253-019-10004-z. Posted with permission.

Copyright Owner

Springer-Verlag GmbH Germany, part of Springer Nature

Language

en

File Format

application/pdf

Published Version

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