1. Volume 8, Issue 4, Pages 329-340 (April 2001)
Molecular basis of Celmer’s rules: role of the ketosynthase domain in epimerisation and demonstration that ketoreductase domains can have altered product specificity with unnatural substrates 
Ines E Holzbaur, Anand Ranganathan, Iain P Thomas, Dominic J.A Kearney, James A Reather, Brian A.M Rudd, James Staunton, Peter F Leadlay 
Chemistry & Biology 
Volume 8, Issue 4, Pages (April 2001)
DOI: /S (01)00014-X

2. Fig. 1
The erythromycin-producing PKS; primary organisation of the genes and their corresponding protein domains. There are six chain extension modules, each beginning with a KS domain, that are responsible for adding the six successive C3 units. The loading module (LM) specifies propionate as the starter unit. The completed chain is released as a macrolactome by the TE domain. KR, β-ketoacyl reductase.
Chemistry & Biology 2001 8, DOI: ( /S (01)00014-X)

3. Fig. 2
Chemistry & Biology 2001 8, DOI: ( /S (01)00014-X)

4. Fig. 3
Comparison of the open chain of the polyketide cores of the related macrolides: (A) methymycin (12 membered macrolide); (B) erythromycin (14-membered macrolide) and; (C) tylosin (16-membered macrolide).
Chemistry & Biology 2001 8, DOI: ( /S (01)00014-X)

5. Fig. 4
Chemistry & Biology 2001 8, DOI: ( /S (01)00014-X)

6. Fig. 5
Arrangement of the domains in: (a) the hybrid PKS TKS–AR1 and; (b) DEBS3.
Chemistry & Biology 2001 8, DOI: ( /S (01)00014-X)

7. Fig. 6
(a) Incubation of the NAC analogue of the keto form of the diketide intermediate of the erythromycin PKS with DEBS3 yields four reduced products. (b) Chiral HPLC trace of the product mixture produced.
Chemistry & Biology 2001 8, DOI: ( /S (01)00014-X)

8. Fig. 7
Stereoelectronics of reduction of a keto group by a KR. The keto group position is determined by coordination to a metal, commonly zinc. Hydride is delivered to either the upper or the lower face depending on the site of binding of the nicotinamide coenzyme (the lower face is arbitrarily selected in this illustration). The stereoselectivity of the reduction process depends on the ability of the active site to discriminate between R1 and R2.
Chemistry & Biology 2001 8, DOI: ( /S (01)00014-X)

9. Fig. 8
Alternative binding modes for the ketone carbonyl of the (R)- and (S)-diketides at the active site of KR5. Hydride reduction takes place at the lower face of the keto group in every case. A combination of all four modes produces all four stereoisomers of the reduction product.
Chemistry & Biology 2001 8, DOI: ( /S (01)00014-X)

10. Fig. 9
Amino acid sequence around the unique HindIII fusion site introduced in the linker regions between the KS and AT domains in ery modules 1 and 5.
Chemistry & Biology 2001 8, DOI: ( /S (01)00014-X)

11. Fig. 10
(a) The total ion current of a typical GC-MS trace of an ethyl acetate extraction of S. erythraea/JC2-p (b) GC-MS selected for m/z=190 corresponding to compounds 3 and 5. (c) GC-MS selected for m/z=176 corresponding to compounds 4 and 6.
Chemistry & Biology 2001 8, DOI: ( /S (01)00014-X)

12. Fig. 11
Condensation and reduction cycles performed by TKS–AR1 in the biosynthesis of compounds 3–6.
Chemistry & Biology 2001 8, DOI: ( /S (01)00014-X)