Identification and investigation of a novel NADP+-dependent secoisolariciresinol dehydrogenase from Isatis indigotica

Xiaoyi Shi; Jiaran Geng; Jingxian Feng; Yingbo Yang; Xueqi Ma; Wansheng Chen; Ying Xiao

doi:10.3389/fpls.2022.1035121

Identification and investigation of a novel NADP⁺-dependent secoisolariciresinol dehydrogenase from Isatis indigotica

Front Plant Sci. 2022 Nov 2:13:1035121. doi: 10.3389/fpls.2022.1035121. eCollection 2022.

Authors

Xiaoyi Shi^{1

2}, Jiaran Geng¹, Jingxian Feng¹, Yingbo Yang^{1

3}, Xueqi Ma¹, Wansheng Chen^{1

4}, Ying Xiao¹

Affiliations

¹ Research and Development Center of Chinese Medicine Resources and Biotechnology, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
² Shanghai Foreign Language School Affiliated to Shanghai International Studies University (SISU), Shanghai, China.
³ Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang, China.
⁴ Department of Pharmacy, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, China.

Abstract

Cofactors are crucial for the biosynthesis of natural compounds, and cofactor engineering is a useful strategy for enzyme optimization due to its potential to enhance enzyme efficiency. Secoisolariciresinol dehydrogenase (SIRD) was reported to convert secoisolariciresinol into matairesinol in an NAD⁺-dependent reaction. Here, a SIRD designated as IiSIRD2 identified from Isatis indigotica was found to utilize NADP⁺ as the cofactor. To explore the structural basis for this unique cofactor preference, model-based structural analysis was carried out, and it was postulated that a variation at the GXGGXG glycine-rich motif of IiSIRD2 alters its cofactor preference. This study paves way for future investigations on SIRD cofactor specificity and cofactor engineering to improve SIRD's catalytic efficiency.

Keywords: Isatis indigotica; cofactor specificity; lignan; matairesinol; secoisolariciresinol dehydrogenase; structural biology.