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On the biosynthesis of barnol, a new phenolic metabolite
PRELIMINARY NOTES
203
This work was supported in part b y the National Science Foundation (NSF GB-I96O ).
Departme~ct of Biochemistry and Nutrition, Virginia Polytechnic Institute, Blacksburg, Vs. (U.S.A.)
S. G. CURSUTT R. R. SCI~MIDT
1 A. L. BAKER AND R. R. SCI-IMIDT, Biochim. Biophys. Acts, 74 (1963) 75. 2 A. L. BAKER AND IR. R. SCI-IMIDT,Biochim. Biophys. Acts, 82 (1964) 336. a S. R, KORNBERG, Biochim. Biophys. Acts, 26 (1957) 294. 4 S. G. CURNUT'r ANI) R. R. SCHMIDT, Exptl. Cell Res., in the press. 5 C. SOROKIN AND J. MYERS, Science, 117 (1953) 33 o. 6 R. R. SCItMIDT AND K. W. KING, Bioehim. Biophys. Act~, 47 (1961) 391. 7 H. U. BERGMEYER, Methods of Enzymatic Analysis, Academic Press, N e w York, 1963, p. 539. 8 H. U. BERGM1*~YER, Methods of Enzymatic Analysis, Academic Press, N e w York, 1963, p. 573. C. H. FISKE AND Y. SUBBMROW, f . Biol. Chem., 66 (1925) 375-
Received J a n u a r y 28th, I964 Biochim. Biophys. Acts, 86 (1964) 2Ol-2O3
PN 21oo5 O n the biosynthesis of barnol, a new phenolic metabolite F r o m the medium of a newly isolated Peuicillium species a novel phenolic compound, barnol, has been isolated and shown to be 5-ethyl-4,6-dimethylpyrogalloP. Investigation of the biosynthesis of this compound gave a somewhat surprising distribution pattern of radioactivity when different precursors were administered (Fig. I). OH HO.. ~ .OH
°CH 2
CH
•
3
]gig. 1. I n this figure, • and O indicate labeling from [I-l~C]acetate a n d E2-14C]acetate, respectively. A c t i v i t y f r o m ~Me-14C]methionine is indicated b y ~k,
As is shown in Table I the basic skeleton of the molecule is derived from 4 acetate units. The same poiyketo structure leading to the formation of orsellinic acid is likely to be an intermediate of barnol as well. In analogy to the established a c e t a t e - p o l y malonate origin of orsellinic acid 2 one m a y thus assume a similar condensation of I acetyl-CoA with 3 malonyl-CoA. I t is noteworthy that the biosynthetic reactions leading to the formation of barnol require the total reduction of a terminal carboxyl group to a methyl group. 2 methionine-derived Cl-units are introduced to the basic acetate-derived moiety. z Cl-unit is directly attached to the benzene ring at position 4, or its equivalent, 6. Biochim. Biophys. Acts, 86 (1964) 203-2o 4
2o4
Pt{ELIMINARY NOTES TABLE ! All v a l u e s g i v e n are c o u n t s / m i n / m m o l e b a r n o l x i o 4. Pyec*¢rso~s Coml>ound [i-zaC]gcetate Barnol
[2-x4C]acetate L-fMe-l*CJmd*io~ine
233~2
x88.6
io27.i
Propionic acid C-I C-2 C-3
6x-3 0.4 0.2
0.8 49.2 0.9
o. 4 o.7 450.3
Acetic acid C-I C-z
0. 4 57.3
91.2 I .o
0. 9 43o.i
The other Cl-unit is added to a methyl group which thus gives rise to the ethyl substituent at position 5- To account for this latter unique methylation at the methyl group, one can think of a qninonemethide as intermediate during methyiationl
Institute of Biochemistry, University of Lund, Lund (S~'ede~)
KLAUS MOSBACH ~NGEMAR L~UNGCRANTZ
1 I. LJUNGCRANTZ AND K. !~VIosBACH,Acta Chem. Scan&, i n t h e press. 2 K. MOSBAClL Naturwissenschaften, 48 (I96I) 525 .
Received J a n u a r y 28th, I964 Biochim. Biophys. •cta, 86 (I964) 203-204
203
This work was supported in part b y the National Science Foundation (NSF GB-I96O ).
Departme~ct of Biochemistry and Nutrition, Virginia Polytechnic Institute, Blacksburg, Vs. (U.S.A.)
S. G. CURSUTT R. R. SCI~MIDT
1 A. L. BAKER AND R. R. SCI-IMIDT, Biochim. Biophys. Acts, 74 (1963) 75. 2 A. L. BAKER AND IR. R. SCI-IMIDT,Biochim. Biophys. Acts, 82 (1964) 336. a S. R, KORNBERG, Biochim. Biophys. Acts, 26 (1957) 294. 4 S. G. CURNUT'r ANI) R. R. SCHMIDT, Exptl. Cell Res., in the press. 5 C. SOROKIN AND J. MYERS, Science, 117 (1953) 33 o. 6 R. R. SCItMIDT AND K. W. KING, Bioehim. Biophys. Act~, 47 (1961) 391. 7 H. U. BERGMEYER, Methods of Enzymatic Analysis, Academic Press, N e w York, 1963, p. 539. 8 H. U. BERGM1*~YER, Methods of Enzymatic Analysis, Academic Press, N e w York, 1963, p. 573. C. H. FISKE AND Y. SUBBMROW, f . Biol. Chem., 66 (1925) 375-
Received J a n u a r y 28th, I964 Biochim. Biophys. Acts, 86 (1964) 2Ol-2O3
PN 21oo5 O n the biosynthesis of barnol, a new phenolic metabolite F r o m the medium of a newly isolated Peuicillium species a novel phenolic compound, barnol, has been isolated and shown to be 5-ethyl-4,6-dimethylpyrogalloP. Investigation of the biosynthesis of this compound gave a somewhat surprising distribution pattern of radioactivity when different precursors were administered (Fig. I). OH HO.. ~ .OH
°CH 2
CH
•
3
]gig. 1. I n this figure, • and O indicate labeling from [I-l~C]acetate a n d E2-14C]acetate, respectively. A c t i v i t y f r o m ~Me-14C]methionine is indicated b y ~k,
As is shown in Table I the basic skeleton of the molecule is derived from 4 acetate units. The same poiyketo structure leading to the formation of orsellinic acid is likely to be an intermediate of barnol as well. In analogy to the established a c e t a t e - p o l y malonate origin of orsellinic acid 2 one m a y thus assume a similar condensation of I acetyl-CoA with 3 malonyl-CoA. I t is noteworthy that the biosynthetic reactions leading to the formation of barnol require the total reduction of a terminal carboxyl group to a methyl group. 2 methionine-derived Cl-units are introduced to the basic acetate-derived moiety. z Cl-unit is directly attached to the benzene ring at position 4, or its equivalent, 6. Biochim. Biophys. Acts, 86 (1964) 203-2o 4
2o4
Pt{ELIMINARY NOTES TABLE ! All v a l u e s g i v e n are c o u n t s / m i n / m m o l e b a r n o l x i o 4. Pyec*¢rso~s Coml>ound [i-zaC]gcetate Barnol
[2-x4C]acetate L-fMe-l*CJmd*io~ine
233~2
x88.6
io27.i
Propionic acid C-I C-2 C-3
6x-3 0.4 0.2
0.8 49.2 0.9
o. 4 o.7 450.3
Acetic acid C-I C-z
0. 4 57.3
91.2 I .o
0. 9 43o.i
The other Cl-unit is added to a methyl group which thus gives rise to the ethyl substituent at position 5- To account for this latter unique methylation at the methyl group, one can think of a qninonemethide as intermediate during methyiationl
Institute of Biochemistry, University of Lund, Lund (S~'ede~)
KLAUS MOSBACH ~NGEMAR L~UNGCRANTZ
1 I. LJUNGCRANTZ AND K. !~VIosBACH,Acta Chem. Scan&, i n t h e press. 2 K. MOSBAClL Naturwissenschaften, 48 (I96I) 525 .
Received J a n u a r y 28th, I964 Biochim. Biophys. •cta, 86 (I964) 203-204