KW - Combinatorial biosynthesis

2016, in press

Insights into complex oxidation during BE-7585A biosynthesis: structural determination and analysis of the polyketide monooxygenase BexE.
Jackson DR, Yu X, Wang G, Patel AB, Barajas JF, Sasaki E, Metsa-Ketala M, Liu HW, Rohr J, Tsai SC.
ACS Chem Biol.

KW - Combinatorial biosynthesis

1. Beynon, J.D.; Rafanan Jr., E.R.; Shen, B.; Fisher, A.J. (2000) Crystallization and Preliminary X-ray Analysis of Tetracenomycin A2 Oxygenase: A Flavoprotein Hydroxylase Involved in Polyketide Biosynthesis. Acta Cryst., D56:1647-1651.
2. Rafanan Jr., E.R.; Hutchinson, C.R.; Shen, B. (2000) Triple Hydroxylation of Tetracenomycin A2 to Tetracenomycin C Involving Two Molecules of O2 and One Molecule of H2O. Org. Lett., 2:3225-3227.
3. Rafanan Jr., E.R.; Le, L.; Zhao, L.; Decker, H.; Shen, B. (2001) Cloning, Sequencing, and Heterologous Expression of the elmGHIJ Genes Involved in the Biosynthesis of the Polyketide Antibiotic Elloramycin from Streptomyces olivaceus Tü2353. J. Nat. Prod., 64:444-449. (Received the 2001 Best Paper Award of J. Nat. Prod.)

Combinatorial Biosynthesis: The Natural Way for Structural Diversity

Examples of Combinatorial Biosynthesis of Pharmaceutical Natural Products

KW - Combinatorial biosynthesis, time-consuming and labor-intensive process- methods and tools in combinatorial biosynthesis, microbiology techniques being far superior

Combinatorial biosynthesis of medicinal plant secondary ..

Baerson; American Chemical Society, 2006.

"Engineered biosynthesis of a novel amidated polyketide using the malonamyl-specific initiation module from the oxytetracycline polyketide synthase" Zhang W, Ames BD, Tsai SC, Tang Y
Applied and Environmental Microbiology 2006, 72, 2573

"Biosynthesis of a 3,6-dideoxyhexose: crystallization and X-ray diffraction of CDP-6-deoxy-threo-glycero-4-hexulose-3-dehydrase (E1) for ascarylose biosynthesis" Smith P, Lin A, Szu P.-h., Liu, H.-w., Tsai SC
Acta Crystal.

Combinatorial and Synthetic Biosynthesis in ..

2006, 188, 477

"Structural enzymology of aromatic polyketide synthase." Korman TP, Ames BD, Tsai, SC In ACS Volume Based on Polyketides: Biosynthesis, Biological Activity and Genetic Engineering.

Combinatorial Biosynthesis of Legume Natural and …

Directed evolution, a powerful enzyme engineering approach, has not been widely employed on natural product biosynthetic enzymes. However, there are significant advantages of applying directed evolution to combinatorial biosynthesis. Compared to more conservative changes by site-specific mutagenesis, directed evolution approaches can potentially spawn more drastic alterations of substrate specificity of domains, while restoring the impaired activity due to large changes in substrate specificity. In contrast to only one enzyme variant obtained with every successful domain swap, directed evolution methods significantly increase the throughput of enzyme variants beneficial for combinatorial biosynthesis. Last but not least, directed evolution can be accomplished even when the enzyme catalytic mechanism still remains elusive.