TY - JOUR

T1 - Biosynthesis of quinolizidine alkaloids in lupins

T2 - mechanistic considerations and prospects for pathway elucidation

AU - Mancinotti, Davide

AU - Frick, Karen Michiko

AU - Geu-Flores, Fernando

PY - 2022

Y1 - 2022

N2 - Covering: up to 2022 Quinolizidine alkaloids (QAs) are a class of alkaloids that accumulate in a variety of leguminous plants and have applications in the agricultural, pharmaceutical and chemical industries. QAs are notoriously present in cultivated lupins (Lupinus spp.) where they complicate the use of the valuable, high-protein beans due to their toxic properties and bitter taste. Compared to many other alkaloid classes, the biosynthesis of QAs is poorly understood, with only the two first pathway enzymes having been discovered so far. In this article, we review the different biosynthetic hypotheses that have been put forth in the literature (1988-2009) and highlight one particular hypothesis (1988) that agrees with the often ignored precursor feeding studies (1964-1994). Our focus is on the biosynthesis of the simple tetracyclic QA (-)-sparteine, from which many of the QAs found in lupins derive. We examine every pathway step on the way to (-)-sparteine and discuss plausible mechanisms, altogether proposing the involvement of 6-9 enzymes. Together with the new resources for gene discovery developed for lupins in the past few years, this review will contribute to the full elucidation of the QA pathway, including the identification and characterization of the missing pathway enzymes.

AB - Covering: up to 2022 Quinolizidine alkaloids (QAs) are a class of alkaloids that accumulate in a variety of leguminous plants and have applications in the agricultural, pharmaceutical and chemical industries. QAs are notoriously present in cultivated lupins (Lupinus spp.) where they complicate the use of the valuable, high-protein beans due to their toxic properties and bitter taste. Compared to many other alkaloid classes, the biosynthesis of QAs is poorly understood, with only the two first pathway enzymes having been discovered so far. In this article, we review the different biosynthetic hypotheses that have been put forth in the literature (1988-2009) and highlight one particular hypothesis (1988) that agrees with the often ignored precursor feeding studies (1964-1994). Our focus is on the biosynthesis of the simple tetracyclic QA (-)-sparteine, from which many of the QAs found in lupins derive. We examine every pathway step on the way to (-)-sparteine and discuss plausible mechanisms, altogether proposing the involvement of 6-9 enzymes. Together with the new resources for gene discovery developed for lupins in the past few years, this review will contribute to the full elucidation of the QA pathway, including the identification and characterization of the missing pathway enzymes.

KW - H-2 NMR-SPECTROSCOPY

KW - NARROW-LEAFED LUPIN

KW - ENZYMATIC-SYNTHESIS

KW - SPARTEINE

KW - LUPANINE

KW - STEREOCHEMISTRY

KW - CADAVERINES

KW - CYTISINE

KW - BAPTISIA

KW - SOPHORA

U2 - 10.1039/d1np00069a

DO - 10.1039/d1np00069a

M3 - Review

C2 - 35302146

VL - 39

SP - 1423

EP - 1437

JO - Natural Product Reports

JF - Natural Product Reports

SN - 0265-0568

IS - 7

ER -