Herboxidiene biosynthesis, production, and structural modifications: prospect for hybrids with related polyketide.
Herboxidiene is a polyketide with a diverse range of activities, including herbicidal, anti-cholesterol, and pre-mRNA splicing inhibitory effects. Thus, production of the compound on the industrial scale is in high demand, and various rational metabolic engineering approaches have been employed to enhance the yield. Directing the precursors and cofactors pool toward the production of polyketide compounds provides a rationale for developing a good host for polyketide production. Due to multiple promising biological activities, the production of a number of herboxidiene derivatives has been attempted in recent years in a search for the key to improve its potency and to introduce new activities. Structural diversification through combinatorial biosynthesis was attempted, utilizing the heterologous expression of substrate-flexible glucosyltransferase (GT) and cytochrome P450 in Streptomyces chromofuscus to generate structurally and functionally diverse derivatives of herboxidiene. The successful attempt confirmed that the strain was amenable to heterologous expression of foreign polyketide synthase (PKS) or post-PKS modification genes, providing the foundation for generating novel or hybrid polyketides.
Department of BT-Convergent Pharmaceutical Engineering, Institute of Biomolecule Reconstruction (iBR), Sun Moon University, 70, Sunmoon-Ro 221, Tangjeong-myeon, Asan, Chungnam, 333-708, Republic of Korea.
Anaya Raj
AR
Pokhrel
Department of BT-Convergent Pharmaceutical Engineering, Institute of Biomolecule Reconstruction (iBR), Sun Moon University, 70, Sunmoon-Ro 221, Tangjeong-myeon, Asan, Chungnam, 333-708, Republic of Korea.
Dipesh
D
Dhakal
Department of BT-Convergent Pharmaceutical Engineering, Institute of Biomolecule Reconstruction (iBR), Sun Moon University, 70, Sunmoon-Ro 221, Tangjeong-myeon, Asan, Chungnam, 333-708, Republic of Korea.
Amit Kumar
AK
Jha
Department of BT-Convergent Pharmaceutical Engineering, Institute of Biomolecule Reconstruction (iBR), Sun Moon University, 70, Sunmoon-Ro 221, Tangjeong-myeon, Asan, Chungnam, 333-708, Republic of Korea. sohng@sunmoon.ac.kr.
Jae Kyung
JK
Sohng
D053898:Biosynthetic Pathways / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D005233:Fatty Alcohols / Q000378:metabolism*; D005964:Glucosyltransferases / Q000235:genetics / Q000378:metabolism; D048630:Polyketide Synthases / Q000235:genetics / Q000378:metabolism; D061065:Polyketides / Q000378:metabolism*; D011714:Pyrans / Q000378:metabolism*; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism*
D005233:Fatty Alcohols; D061065:Polyketides; D011714:Pyrans; C076087:herboxidiene; D048630:Polyketide Synthases; D003577:Cytochrome P-450 Enzyme System; D005964:Glucosyltransferases
Combinatorial biosynthesis; Enhancement; Herboxidiene; Hybrid polyketide; Polyketide