Biosynthetic studies of coronatine and polyoximic acid.

摘要

Coronatine (1) (Fig 1) is a novel, non-host specific phytotoxin elaborated in the liquid fermentation broths of several different Pseudomonas syringae pathovers. Infection of tomato plants by P. syringae pv. {dollar}tomato,sp1{dollar} Italian ryegrass by P. syringae pv. {dollar}atropurpurea,sp{lcub}2,3{rcub}{dollar} soybean by P. syringae pv. {dollar}glycinae,sp{lcub}3,4{rcub}{dollar} and Prunus spp. by P. syringae pv. {dollar}morsprunorumsp3{dollar} induces yellow chlorotic haloes, stunting, and plant tissue hypertrophy due to the production of coronatine.{dollar}sp{lcub}2,4{rcub}{dollar} Coronatine presents two distinct biosynthetic problems, one being the origin of coronafacic acid (2) the other the origin of the novel amino acid coronamic acid (3) (Fig 1). The investigations presented in this dissertation were directed towards an understanding of the biosynthetic pathway to coronamic acid. Our results from the administration of specifically labeled precursors to Pseudomonas syringae pv. glycinae (PDCC # 4182) suggest that: (1) the retention of the tritium label from (3-{dollar}sp3{dollar}H) -L-alloisoleucine rules out the intermediacy of 3-methylene-norvaline on the biosynthetic pathway to coronamic acid, (2) the incorporation of approximately half of the {dollar}sp{lcub}15{rcub}{dollar}N label from a mixture of (2-{dollar}sp{lcub}13{rcub}{dollar}C, {dollar}sp{lcub}15{rcub}{dollar}N)-DL-isoleucine and (2-{dollar}sp{lcub}13{rcub}{dollar}C, {dollar}sp{lcub}15{rcub}{dollar}N)-DL-alloisoleucine indicates that the cyclisation reaction leading to the formation of coronamic acid from L-alloisoleucine does not involve the loss of nitrogen and (3) the incorporation of (4-{dollar}sp2{dollar}H{dollar}sb1{dollar},5-{dollar}sp2{dollar}H{dollar}sb1{dollar})-({dollar}pm{dollar})-coronamic acid provides some experimental evidence in support of the hypothesis that coronamic acid and coronafacic acid are biosynthesised separately and coupled by the formation of an amide bond to give coronatine.; Polyoximic acid (8) (Fig 4) is the amino acid component of polyoxins A, F, H, I, and K, a unique class of antifungal antibiotics elaborated in the fermentation broths of Streptomyces cacaoi var. {dollar}asoensis.sp{lcub}20,22,37{rcub}{dollar} Our investigations presented in this dissertation on the biosynthetic origin of polyoximic acid by the administration of specifically labeled precursors to Streptomyces cacaoi var. asoensis (ATCC # 19094) suggest that: (1) polyoximic acid is biosynthetically derived from L-isoleucine, (2) the incorporation of the {dollar}sp{lcub}13{rcub}{dollar}C label from (1-{dollar}sp{lcub}13{rcub}{dollar}C)-L-alloisoleucine into C-1" of polyoximic acid requires that the formation of the exocyclic double bond of polyoximic acid be formed by a syn-elimination of hydrogen from C-3 and not an anti-elimination as previously reported{dollar}sp{lcub}38{rcub}{dollar} and (3) the retention of two deuterium atoms, at C-4" of polyoximic acid derived from (6-{dollar}sp{lcub}13{rcub}{dollar}C,{dollar}sp2{dollar}H{dollar}sb3{dollar})-DL-isoleucine and (6-{dollar}sp{lcub}13{rcub}{dollar}C,{dollar}sp2{dollar}H{dollar}sb3{dollar})-DL-alloisoleucine, indicates that the cyclisation reaction requires the loss of only one hydrogen atom from L-isoleucine and L-alloisoleucine.