Hutchinson's legacy: keeping on polyketide biosynthesis

Abstract

Professor Charles Richard Hutchinson (Hutch) dedicated his research to the study of polyketide compounds, in particular, those produced by actinomycetes. Hutch principally centered his efforts to study the biosynthesis of bioactive compounds, antibiotic and antitumor drugs, and to develop new derivatives with improved therapeutic properties. After dedicating 40 years to the study of polyketides, Hutch leaves us, as legacy, the knowledge that he and his collaborators have accumulated and shared with the scientific community. The best tribute we can offer to him is keeping on the study of polyketides and other bioactive compounds, in an effort to generate more safer and useful drugs. In this review, the work on the polyketides, borrelidin, steffimycin and streptolydigin, performed at the laboratory of Professors Salas and Mé ndez at University of Oviedo (Spain) during the last 10 years, is summarized.

One-Pot Enzymatic Total Synthesis of Presteffimycinone, an Early Intermediate of the Anthracycline Antibiotic Steffimycin Biosynthesis

“…Steffimycin ( 5 ), which was first isolated in 1967 from Streptomyces steffiburgensis , is an unusual anthracycline-type antitumor antibiotic because of its rich decoration with oxygen atoms in rings A and D . The compound has been shown to induce DNA damage, thus inducing high apoptotic response in p53-expressing HCT116 colon carcinoma cells; several derivatives of steffimycin or chemically modified analogues also showed good carcinoma-repression effects . Steffimycin contains several unique structural features that are absent in other anthracyclines, including the C10 keto group, two methoxy groups (C2 and C8), and a neutral deoxysugar instead of the more typical aminosugar (Scheme ).…”

Cyclosporines: Biosynthesis and Beyond

“…In line with our contemporary understanding of type II polyketide biosynthesis [90][91][92][93][94][95], Bmt biosynthesis is most likely elaborated over two stages: (1) the basic assembly of the polyketide backbone via the head-to-tail condensation of four acetate units, which involves reduction and dehydration and methylation reactions; (2) the transformation process into the final Bmt product, which involves incorporation of the amino group. Offenzeller et al [96] performed detailed in vivo labeling experiments and in vitro polyketide synthesis assays with enriched enzyme fractions from T. inflatum strain NRRL 8044, which identified 3(R)-hydroxy-4(R)-methyl-6(E)-octenoyl-CoA as the end-product of the basic assembly process.…”

Biotechnology of polyketides: new breath of life for the novel antibiotic genetic pathways discovery through metagenomics

“…One of the foremost scientists involved in studying PKSs was Professor Charles Richard Hutchinson who dedicated a part of his life to conducting detailed studies on these important classes of enzymes (The Journal of Antibiotics, 2011; Olano, 2011). The death of Dr. Hutchinson on January 5, 2010 was undoubtedly a great loss to academic research in this field.…”

“…The death of Dr. Hutchinson on January 5, 2010 was undoubtedly a great loss to academic research in this field. The legacy of Dr. Hutchinson (Olano, 2011) and the results of 40 years dedicated to PKS studies involving the search for new drugs, particularly against cancer (ironically, the disease that killed him at age 66) include the study of bacterial and fungal polyketides. Among the type I PKSs, Hutchinson and colleagues studied the erythromycin, geldanamycin, herbimycin, lasalocid, megalomycin, midecamycin, rapamycin and rifamycin synthesis pathways.…”