Open AccessEnhanced bioproduction of anticancer precursor vindoline by yeast cell factories
Author(s) -
Kulagitalja,
Guirimand Grégory,
Melin Céline,
LemosCruz Pamela,
Carqueijeiro Ines,
De Craene JohanOwen,
Oudin Audrey,
Heredia Vladimir,
Koudounas Konstantinos,
Unlubayir Marianne,
Lanoue Arnaud,
Imbault Nadine,
StPierre Benoit,
Papon Nicolas,
Clastre Marc,
GiglioliGuivarc’h Nathalie,
Marc Jillian,
Besseau Sébastien,
Courdavault Vincent
Publication year - 2021
Publication title -
microbial biotechnology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.287
H-Index - 74
ISSN - 1751-7915
DOI - 10.1111/1751-7915.13898
Subject(s) - bioproduction , vindoline , vinblastine , yeast , microbiology and biotechnology , bioreactor , chemistry , bioprocess , biology , pulp and paper industry , biochemistry , botany , paleontology , genetics , chemotherapy , engineering
Summary The pharmaceutical industry faces a growing demand and recurrent shortages in many anticancer plant drugs given their extensive use in human chemotherapy. Efficient alternative strategies of supply of these natural products such as bioproduction by microorganisms are needed to ensure stable and massive manufacturing. Here, we developed and optimized yeast cell factories efficiently converting tabersonine to vindoline, a precursor of the major anticancer alkaloids vinblastine and vincristine. First, fine‐tuning of heterologous gene copies restrained side metabolites synthesis towards vindoline production. Tabersonine to vindoline bioconversion was further enhanced through a rational medium optimization (pH, composition) and a sequential feeding strategy. Finally, a vindoline titre of 266 mg l −1 (88% yield) was reached in an optimized fed‐batch bioreactor. This precursor‐directed synthesis of vindoline thus paves the way towards future industrial bioproduction through the valorization of abundant tabersonine resources.