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SECTION I: MOLECULAR GENETIC ENGINEERING AND BIOCHEMICAL TECHNOLOGY 41The biosynthetic pathway of herboxidiene from S. chromofuscus ATCC 49982 was reported by Shao et al. (2012). They sequenced the genome of S. chromofuscus, producing 9.6 Mb of sequence data (unpublished), and identified a 53 kb gene cluster containing seven open reading frames (ORFs) responsible for herboxidiene biosynthesis. This cluster encodes a type I polyketide synthase (PKS) system, where three ORFs code for a multimodular type I PKS with nine modules; the first module acts as a loading module [4]. Like most of the bacterial type I PKS, herboxidiene PKS also works on a modular fashion with each module for one round of chain elongation and optional reduction steps before the transfer of processed chain to downstream module. The polyketide chain is translocated continuously until the final cycle of elongation which follows the release of polyketide chain from the PKS by hydrolysis. The chain release is followed by suggested subsequent 3,7 - cyclization of the linear nonaketide chain to giving rise to a tetrahydropyran (THP) ring, most likely in a spontaneous process [4]. This also suggests the absence of role of TE in THP ring formation. The correlation between polyketide chain and domain organization of PKS is known as co-linearity [5]. Herboxidiene PKS contains total of six DH domains; one domain each in module 2, 3, 4, 5, 7 and 8. The ER domain is present only in modules 3 and 7. All of the catalytic domains described above are responsible for the reduction of intermediates on a linear 19 - carbon nonaketide, which is finally released from polyketide synthase by the thioesterase (TE) domain present at the end of module 8 [6]. Numerous breakthroughs in polyketide biosynthesis have been made possible by the co-linearity between the arrangement of PKS genes and the structure of polyketides, enabling the prediction of biosynthetic schemes