Open AccessThe Stereochemistry of β‐Lactam Formation in Penicillin Biosynthesis
Author(s) -
YOUNG Douglas W.,
SEN Prabir K.,
MORECOMBE Donald J.
Publication year - 1977
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1977.tb11511.x
Subject(s) - tritium , penicillin , chemistry , penicillium chrysogenum , cystine , stereospecificity , stereochemistry , cysteine , lactam , organic chemistry , catalysis , antibiotics , biochemistry , enzyme , physics , nuclear physics
1 (2 R ,3 S )‐[U‐ 14 C,3‐ 3 H 1 ]‐ and (2 R ,3 R )‐[U‐ 14 C,2,3‐ 3 H 2 ] Cysteine hydrochlorides have been separately synthesised. The latter compound has been shown to have uniform distribution of tritium between C‐2 and C‐3. 2 The above cysteines and (2 R )‐[U‐ 14 C,3,3,3′,3′‐ 3 H 4 ]cystine have been converted to samples of penicillin G by Penicillium chrysogenum . 3 Incorporation results indicate that all but 14% of the tritium is lost from the (2 R ,3 S )‐[3‐ 3 H 1 ]isomer; that 42% of tritium is retained by the non‐stereospecifically C‐3 tritiated cystine; and that 58% of tritium is retained by the (2 R ,3 R )‐[2,3‐ 3 H 2 ]isomer on conversion to penicillin G. 4 Degradation of the penicillin G derived from (2 R ,3 R )‐[U‐ 14 C,2,3‐ 3 H 2 ]cysteine hydrochloride has indicated that in fact about 87% of the original C‐3 tritium of cysteine is retained at C‐5 of penicillin G. 5 The results indicate stereospecificity in the cyclisation giving rise to the β‐lactam ring in penicillin G in nature with loss of the 3‐ pro ‐ S ‐hydrogen and retention of the 3‐ pro ‐ R ‐hydrogen of cysteine. Thus there is net retention of stereochemistry in the cyclisation.