The herbicidal natural product phosphonothrixin is an inhibitor of the riboflavin biosynthetic enzyme L-3,4-dihydroxy-2-butanone-4-phosphate synthase.

BACKGROUND

In our ongoing search for new and environmentally friendly chemical entities that can control weeds via new modes of action we reinvestigated the herbicidal potency of the natural phytotoxin phosphonothrixin and researched its mode of action.

RESULTS

Phosphonothrixin displayed broad but non-selective post-emergence herbicidal in vivo activity in greenhouse tests, albeit at high application rates. Based on a hypothesis on its mechanism of action derived from a literature study we demonstrated that phosphonothrixin significantly increased the thermostability of 3,4-dihydroxy-2-butanone-4-phosphate synthase (DHBPS), an enzyme involved in riboflavin (vitamin B2) biosynthesis and inhibited the enzyme competitively with respect to its substrate D-ribose-5-phosphate. Inhibition of DHBPS as the mode of action of phosphonothrixin was confirmed by the elucidation of the X-ray crystal structure of DHBPS in complex with phosphonothrixin and Mg-ions.

CONCLUSION

The natural phytotoxin phosphonothrixin is the first herbicide inhibiting an enzyme involved in vitamin B2 (riboflavin) biosynthesis and represents a prototype of a novel herbicide with a brand-new mode of action. © 2025 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.