Publication result detail

Engineering of UGT86C11 glycosyltransferase for improving catalytic efficiency and efficient biosynthesis of neoandrographolide

SRIVASTAVA, P.; VYAS, P.; KUMAR, A.; BHOGAL, I.; GHOSH, S.; ROY, S.

Original Title

Engineering of UGT86C11 glycosyltransferase for improving catalytic efficiency and efficient biosynthesis of neoandrographolide

English Title

Engineering of UGT86C11 glycosyltransferase for improving catalytic efficiency and efficient biosynthesis of neoandrographolide

Type

WoS Article

Original Abstract

Neoandrographolide is a bioactive diterpenoid biosynthesized in the medicinal plant Andrographis paniculata by the C19-O-glycosyltransferase UGT86C11. Neoandrographolide supply typically suffers owing to inadequate amounts in A. paniculata, highlighting the need for an efficient bioprocess to produce this compound. We combined computational modeling of UGT86C11 structure and diterpenoid binding dynamics with site-directed mutagenesis and developed UGT86C11 variants (E163A, T403A and F404A) having ~2-fold increased catalytic efficiency. E163A, T403A and F404A displayed increased turnover of C19-O-glycosylation reaction. Moreover, T403A and F404A showed higher affinity for UDP-glucose sugar donor. Escherichia coli expression of UGT86C11 variants, coupled with an improved UDP-glucose regeneration system enabled a remarkable biotransformation rate of neoandrographolide, reaching up to 91% conversion as compared to ~45% using native UGT86C11. Besides, UGT86C11 variants demonstrated ~6-fold higher neoandrographolide biosynthesis in Nicotiana benthamiana. Thus, the engineered UGT86C11 presents a promising avenue for the efficient production of neoandrographolide utilizing both plant and microbial hosts.

English abstract

Neoandrographolide is a bioactive diterpenoid biosynthesized in the medicinal plant Andrographis paniculata by the C19-O-glycosyltransferase UGT86C11. Neoandrographolide supply typically suffers owing to inadequate amounts in A. paniculata, highlighting the need for an efficient bioprocess to produce this compound. We combined computational modeling of UGT86C11 structure and diterpenoid binding dynamics with site-directed mutagenesis and developed UGT86C11 variants (E163A, T403A and F404A) having ~2-fold increased catalytic efficiency. E163A, T403A and F404A displayed increased turnover of C19-O-glycosylation reaction. Moreover, T403A and F404A showed higher affinity for UDP-glucose sugar donor. Escherichia coli expression of UGT86C11 variants, coupled with an improved UDP-glucose regeneration system enabled a remarkable biotransformation rate of neoandrographolide, reaching up to 91% conversion as compared to ~45% using native UGT86C11. Besides, UGT86C11 variants demonstrated ~6-fold higher neoandrographolide biosynthesis in Nicotiana benthamiana. Thus, the engineered UGT86C11 presents a promising avenue for the efficient production of neoandrographolide utilizing both plant and microbial hosts.

Keywords

UDP-glycosyltransferase, diterpenoid, site-directed mutagenesis, protein structural modeling, enzyme kinetics, neoandrographolide, biotransformation

Key words in English

UDP-glycosyltransferase, diterpenoid, site-directed mutagenesis, protein structural modeling, enzyme kinetics, neoandrographolide, biotransformation

Authors

SRIVASTAVA, P.; VYAS, P.; KUMAR, A.; BHOGAL, I.; GHOSH, S.; ROY, S.

RIV year

2026

Released

09.12.2025

Periodical

Journal of Agricultural and Food Chemistry

Volume

73

Number

51

State

United States of America

Pages from

32723

Pages to

32739

Pages count

17

URL

https://pubs.acs.org/doi/10.1021/acs.jafc.5c04608

BibTex

@article{BUT199663,
  author="{} and  {} and  {} and Inderjeet {Bhogal} and  {} and Sudeep {Roy}",
  title="Engineering of UGT86C11 glycosyltransferase for improving catalytic efficiency and efficient biosynthesis of neoandrographolide",
  journal="Journal of Agricultural and Food Chemistry",
  year="2025",
  volume="73",
  number="51",
  pages="32723--32739",
  doi="10.1021/acs.jafc.5c04608",
  issn="0021-8561",
  url="https://pubs.acs.org/doi/10.1021/acs.jafc.5c04608"
}