Submitted to: Applied and Environmental Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/27/2003
Publication Date: 6/1/2003
Citation: GLENN, A.E., MEREDITH, F.I., MORRISON III, W.H., BACON, C.W. 2003. IDENTIFICATION OF INTERMEDIATE AND BRANCH METABOLITES RESULTING FROM BIOTRANSFORMATION OF 2-BENZOXAZOLINONE (BOA) BY FUSARIUM VERTICILLIOIDES. APPLIED AND ENVIRONMENTAL MICROBIOLOGY. v.69(6). p.3165-3169.
Interpretive Summary: During the natural development of corn plants, chemical compounds are produced within the plant cells that act as insect feeding deterrents and antimicrobials against plant pathogens. These compounds are commonly referred to as DIMBOA, DIBOA, MBOA, and BOA. Despite the presence of these compounds, essentially all corn grown throughout the world is infected with the fungus Fusarium verticillioides. Infection of corn plants by this fungus is of concern because it produces a class of mycotoxins called fumonisins that are detrimental to the health of animals and potentially humans, and these fumonisins can accumulate and contaminate corn and corn products. Thus, the more we know about how this fungus infects and colonizes corn plants and how it responds to the plant's defensive responses, the more likely resistant corn plants can be developed. Prior research has shown F. verticillioides has the genetic and physiological capacity to detoxify, or biotransform, the plant's antimicrobials into non-toxic compounds. In this study we expand upon the previous work and present evidence for the identity of an intermediate (=2-aminophenol) and a branch metabolite (=2-acetamidophenol) involved in the pathway for biotranformation of BOA into the non-toxic compound N-(2-hydroxyphenyl) malonamic acid. Detoxification of the related antimicrobial MBOA to produce N-(2-hydroxy-4-methoxyphenyl) malonamic acid (HMPMA) is hypothesized to also occur via the same enzymatic modifications. The possibility that biotransformation could be an ecological fitness factor is discussed. Such biotransformation may help to explain why F. verticillioides is the dominant fungus occurring in cornfield environments, and this study provides greater detail on the enzymatic and chemical processes involved and could facilitate future research focused on isolation and identification of metabolites from field samples.
Technical Abstract: Detoxification of the maize (Zea mays) antimicrobial compound 2-benzoxazolinone (BOA) by Fusarium verticillioides involves two genetic loci, FDB1 and FDB2, and results in the formation of N-(2-hydroxyphenyl) malonamic acid (HPMA). Intermediate and branch metabolites were previously suggested to be part of the biotransformation pathway. Evidence is presented here in support of 2-aminophenol as the intermediate metabolite and 2-acetamidophenol as the branch metabolite, which was previously denoted as BOA-X. Overall, metabolism of BOA is suggested to involve hydrolysis (FDB1) to produce 2-aminophenol, which is then modified (FDB2) by addition of a malonyl group to produce HPMA. If the modification is prevented due to genetic mutation (fbd2), then 2-acetamidophenol can accumulate to a minor degree as a result of addition of an acetyl group to 2-aminophenol. Detoxification of the related antimicrobial 6-methoxy-2-benzoxazolinone (MBOA) to produce N-(2-hydroxy-4-methoxyphenyl) malonamic acid (HMPMA) is hypothesized to also occur via the same enzymatic modifications.