Polyketide

Last updated

In organic chemistry, polyketides are a class of natural products derived from a precursor molecule consisting of a chain of alternating ketone (>C=O, or its reduced forms) and methylene (>CH2) groups: [−C(=O)−CH2−]n. [1] First studied in the early 20th century, discovery, biosynthesis, and application of polyketides has evolved. It is a large and diverse group of secondary metabolites caused by its complex biosynthesis which resembles that of fatty acid synthesis. Because of this diversity, polyketides can have various medicinal, agricultural, and industrial applications. Many polyketides are medicinal or exhibit acute toxicity. Biotechnology has enabled discovery of more naturally-occurring polyketides and evolution of new polyketides with novel or improved bioactivity.

Contents

History

Naturally produced polyketides by various plants and organisms have been used by humans since before studies on them began in the 19th and 20th century. In 1893, J. Norman Collie synthesized detectable amounts of orcinol by heating dehydracetic acid with barium hydroxide causing the pyrone ring to open into a triketide. [2] Further studies in 1903 by Collie on the triketone polyketide intermediate noted the condensation occurring amongst compounds with multiple keten groups coining the term polyketides. [3]

Biosynthesis of orsellinic acid from polyketide intermediate. Orsellinsaure is.svg
Biosynthesis of orsellinic acid from polyketide intermediate.

It wasn't until 1955 that the biosynthesis of polyketides were understood. [4] Arthur Birch used radioisotope labeling of carbon in acetate to trace the biosynthesis of 2-hydroxy-6-methylbenzoic acid in Penicillium patulum and demonstrate the head-to-tail linkage of acetic acids to form the polyketide. [5] In the 1980s and 1990s, advancements in genetics allowed for isolation of the genes associated to polyketides to understand the biosynthesis. [4]

Discovery

Polyketides can be produced in bacteria, fungi, plants, and certain marine organisms. [6] Earlier discovery of naturally occurring polyketides involved the isolation of the compounds being produced by the specific organism using organic chemistry purification methods based on bioactivity screens. [7] Later technology allowed for the isolation of the genes and heterologous expression of the genes to understand the biosynthesis. [8] In addition, further advancements in biotechnology have allowed for the use of metagenomics and genome mining to find new polyketides using similar enzymes to known polyketides. [9]

Biosynthesis

Polyketides are synthesized by multienzyme polypeptides that resemble eukaryotic fatty acid synthase but are often much larger. [4] They include acyl-carrier domains plus an assortment of enzymatic units that can function in an iterative fashion, repeating the same elongation/modification steps (as in fatty acid synthesis), or in a sequential fashion so as to generate more heterogeneous types of polyketides. [10]

Biosynthesis of carminic acid Biosynthesis of carminic acid.jpg
Biosynthesis of carminic acid

Polyketide synthase

Polyketides are produced by polyketide synthases (PKSs). The core biosynthesis involves stepwise condensation of a starter unit (typically acetyl-CoA or propionyl-CoA) with an extender unit (either malonyl-CoA or methylmalonyl-CoA). The condensation reaction is accompanied by the decarboxylation of the extender unit, yielding a beta-keto functional group and releasing a carbon dioxide. [10] The first condensation yields an acetoacetyl group, a diketide. Subsequent condensations yield triketides, tetraketide, etc. [11] Other starter units attached to a coezyme A include isobutyrate, cyclohexanecarboxylate, malonate, and benzoate. [12]

PKSs are multi-domain enzymes or enzyme complex consisting of various domains. The polyketide chains produced by a minimal polyketide synthase (consisting of a acyltransferase and ketosynthase for the stepwise condensation of the starter unit and extender units) are almost invariably modified. [13] Each polyketide synthases is unique to each polyketide chain because they contain different combinations of domains that reduce the carbonyl group to a hydroxyl (via a ketoreductase), an olefin (via a dehydratase), or a methylene (via an enoylreductase). [14]

Termination of the polyketide scaffold biosynthesis can also vary. It is sometimes accompanied by a thioesterase that releases the polyketide via hydrating the thioester linkage (as in fatty acid synthesis) creating a linear polyketide scaffold. However, if water is not able to reach the active site, the hydrating reaction will not occur and an intramolecular reaction is more probable creating a macrocyclic polyketide. Another possibility is spontaneous hydrolysis without the aid of a thioesterase. [15]

Post-tailoring enzymes

Further possible modifications to the polyketide scaffolds can be made. This can include glycosylation via a glucosyltransferase or oxidation via a monooxygenase. [16] Similarly, cyclization and aromatization can be introduced via a cyclase, sometimes proceeded by the enol tautomers of the polyketide. [17] These enzymes are not part of the domains of the polyketide synthase. Instead, they are found in gene clusters in the genome close to the polyketide synthase genes. [18]

Classification

Polyketides are a structurally diverse family. [19] There are various subclasses of polyketides including: aromatics, macrolactones/macrolides, decalin ring containing, polyether, and polyenes. [15]

Polyketide synthases are also broadly divided into three classes: Type I PKSs (multimodular megasynthases that are non-iterative, often producing macrocodes, polyethers, and polyenes), Type II PKSs (dissociated enzymes with iterative action, often producing aromatics), and Type III PKSs (chalcone synthase-like, producing small aromatic molecules). [20]

In addition to these subclasses, there also exist polyketides that are hybridized with nonribosomal peptides (Hybrid NRP-PK and PK-NRP). Since nonribosomal peptide assembly lines use carrier proteins similar to those use in polyketide synthases, convergence of the two systems evolved to form hybrids, resulting in polypeptides with nitrogen in the skeletal structure and complex function groups similar to those found in amino acids. [21]

Applications

Polyketide antibiotics, [22] antifungals, [23] cytostatics, [24] anticholesteremic, [25] antiparasitics, [23] coccidiostats, animal growth promoters and natural insecticides [26] are in commercial use.

Medicinal

There are more than 10,000 known polyketides, 1% of which are known to have potential for drug activity. [27] Polyketides comprise 20% of the top-selling pharmaceuticals with combined worldwide revenues of over USD 18 billion per year. [28]

Polyketides
Geldanamycin.svg Doxycycline.svg Erythromycin A.svg (-)-Aflatoxin B1 Structural Formulae V.1.svg
Geldanamycin, an antibiotic. Doxycycline, an antibiotic. Erythromycin, an antibiotic. Aflatoxin B1 known carcinogenic compound.

Examples

Agricultural

Polyketides can be used for crop protection as pesticides. [31]

Examples

Industrial

Polyketides can be used for industrial purposes, such as pigmentation [32] and dietary flavonoids. [33]

Examples

Biotechnology

Protein engineering has opened avenues for creating polyketides not found in nature. For example, the modular nature of PKSs allows for domains to be replaced, added or deleted. Introducing diversity in assembly lines enables the discovery of new polyketides with increased bioactivity or new bioactivity. [21]

Furthermore, the use of genome mining allows for discovery of new natural polyketides and their assembly lines. [9]

See also

Related Research Articles

<span class="mw-page-title-main">Alamethicin</span> Chemical compound

Alamethicin is a channel-forming peptide antibiotic, produced by the fungus Trichoderma viride. It belongs to peptaibol peptides which contain the non-proteinogenic amino acid residue Aib. This residue strongly induces formation of alpha-helical structure. The peptide sequence is

<span class="mw-page-title-main">Oxytetracycline</span> Antibiotic

Oxytetracycline is a broad-spectrum tetracycline antibiotic, the second of the group to be discovered.

Nonribosomal peptides (NRP) are a class of peptide secondary metabolites, usually produced by microorganisms like bacteria and fungi. Nonribosomal peptides are also found in higher organisms, such as nudibranchs, but are thought to be made by bacteria inside these organisms. While there exist a wide range of peptides that are not synthesized by ribosomes, the term nonribosomal peptide typically refers to a very specific set of these as discussed in this article.

Polyketide synthases (PKSs) are a family of multi-domain enzymes or enzyme complexes that produce polyketides, a large class of secondary metabolites, in bacteria, fungi, plants, and a few animal lineages. The biosyntheses of polyketides share striking similarities with fatty acid biosynthesis.

<span class="mw-page-title-main">Chalcone synthase</span>

Chalcone synthase or naringenin-chalcone synthase (CHS) is an enzyme ubiquitous to higher plants and belongs to a family of polyketide synthase enzymes (PKS) known as type III PKS. Type III PKSs are associated with the production of chalcones, a class of organic compounds found mainly in plants as natural defense mechanisms and as synthetic intermediates. CHS was the first type III PKS to be discovered. It is the first committed enzyme in flavonoid biosynthesis. The enzyme catalyzes the conversion of 4-coumaroyl-CoA and malonyl-CoA to naringenin chalcone.

<span class="mw-page-title-main">Biosynthesis of doxorubicin</span>

Doxorubicin (DXR) is a 14-hydroxylated version of daunorubicin, the immediate precursor of DXR in its biosynthetic pathway. Daunorubicin is more abundantly found as a natural product because it is produced by a number of different wild type strains of streptomyces. In contrast, only one known non-wild type species, streptomyces peucetius subspecies caesius ATCC 27952, was initially found to be capable of producing the more widely used doxorubicin. This strain was created by Arcamone et al. in 1969 by mutating a strain producing daunorubicin, but not DXR, at least in detectable quantities. Subsequently, Hutchinson's group showed that under special environmental conditions, or by the introduction of genetic modifications, other strains of streptomyces can produce doxorubicin. His group has also cloned many of the genes required for DXR production, although not all of them have been fully characterized. In 1996, Strohl's group discovered, isolated and characterized dox A, the gene encoding the enzyme that converts daunorubicin into DXR. By 1999, they produced recombinant Dox A, a Cytochrome P450 oxidase, and found that it catalyzes multiple steps in DXR biosynthesis, including steps leading to daunorubicin. This was significant because it became clear that all daunorubicin producing strains have the necessary genes to produce DXR, the much more therapeutically important of the two. Hutchinson's group went on to develop methods to improve the yield of DXR, from the fermentation process used in its commercial production, not only by introducing Dox A encoding plasmids, but also by introducing mutations to deactivate enzymes that shunt DXR precursors to less useful products, for example baumycin-like glycosides. Some triple mutants, that also over-expressed Dox A, were able to double the yield of DXR. This is of more than academic interest because at that time DXR cost about $1.37 million per kg and current production in 1999 was 225 kg per annum. More efficient production techniques have brought the price down to $1.1 million per kg for the non-liposomal formulation. Although DXR can be produced semi-synthetically from daunorubicin, the process involves electrophilic bromination and multiple steps and the yield is poor. Since daunorubicin is produced by fermentation, it would be ideal if the bacteria could complete DXR synthesis more effectively.

In enzymology, an erythronolide synthase is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Codinaeopsin</span> Chemical compound

Codinaeopsin is an antimalarial isolated from a fungal isolate found in white yemeri trees (Vochysia guatemalensis) in Costa Rica. It is reported to have bioactivity against Plasmodium falciparum with an IC50 = 2.3 μg/mL (4.7 μM). Pure codinaeopsin was reported to be isolated with a total yield of 18 mg/mL from cultured fungus. The biosynthesis of codinaeopsin involves a polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) hybrid.

<span class="mw-page-title-main">Germicidin</span> Chemical compound

Germicidins are a groups of natural products arising from Streptomyces species that acts as autoregulatory inhibitor of spore germination. In Streptomyces viriochromogenes, low concentrations inhibit germination of its own arthrospores, and higher concentrations inhibit porcine Na+/K+ -activated ATPase. Inhibitory effects on germination are also observed when germicidin from Streptomyces is applied to Lepidium sativum. Germicidins and other natural products present potential use as pharmaceuticals, and in this case, those with possible antibiotic or antifungal activity.

<span class="mw-page-title-main">Debromomarinone</span> Chemical compound

Debromomarinone is a chemical compound isolated from marine actinomycetes.

<span class="mw-page-title-main">Marinone</span> Chemical compound

Marinone is an antibiotic made by marine actinomycetes.

Curcumin synthase categorizes three enzyme isoforms, type III polyketide synthases (PKSs) present in the leaves and rhizome of the turmeric plant that synthesize curcumin. CURS1-3 are responsible for the hydrolysis of feruloyldiketide-CoA, previously produced in the curcuminoid pathway, and a decarboxylative condensation reaction that together comprise one of the final steps in the synthesis pathway for curcumin, demethoxycurcumin, and bisdemethoxycurcumin, the compounds that give turmeric both its distinctive yellow color, and traditional medical benefits. CURS should not be confused with Curcuminoid Synthase (CUS), which catalyzes the one-pot synthesis of bisdemethoxycurcumin in Oryza sativa.

<span class="mw-page-title-main">Atrop-abyssomicin C</span> Chemical compound

Atrop-abyssomicin C is a polycyclic polyketide-type natural product that is the atropisomer of abyssomicin C. It is a spirotetronate that belongs to the class of tetronate antibiotics, which includes compounds such as tetronomycin, agglomerin, and chlorothricin. In 2006, the Nicolaou group discovered atrop-abyssomicin C while working on the total synthesis of abyssomicin C. Then in 2007, Süssmuth and co-workers isolated atrop-abyssomicin C from Verrucosispora maris AB-18-032, a marine actinomycete found in sediment of the Japanese sea. They found that atrop-abyssomicin C was the major metabolite produced by this strain, while abyssomicin C was a minor product. The molecule displays antibacterial activity by inhibiting the enzyme PabB, thereby depleting the biosynthesis of p-aminobenzoate.

<i>BY1</i> Species of fungus

BY1 is a taxonomically unidentified basidiomycete fungus. ITS sequencing has placed it in the Russulales and is referred to as a stereaceous basidiomycete. Chemotaxonomically supporting its placement in this group, it produces fomannoxins and vibralactones. The fungus' mycelia were isolated from dead aspen in Minnesota, USA. It is presumed to decompose wood by white rot.

<span class="mw-page-title-main">C-1027</span> Chemical compound

C-1027 or lidamycin is an antitumor antibiotic consisting of a complex of an enediyne chromophore and an apoprotein. It shows antibiotic activity against most Gram-positive bacteria. It is one of the most potent cytotoxic molecules known, due to its induction of a higher ratio of DNA double-strand breaks than single-strand breaks.

Butyrolactol A is an organic chemical compound of interest for its potential use as an antifungal antibiotic.

<span class="mw-page-title-main">Dihydromaltophilin</span> Chemical compound

Dihydromaltophilin, or heat stable anti-fungal factor (HSAF), is a secondary metabolite of Streptomyces sp. and Lysobacter enzymogenes. HSAF is a polycyclic tetramate lactam containing a single tetramic acid unit and a 5,5,6-tricyclic system. HSAF has been shown to have anti-fungal activity mediated through the disruption of the biosynthesis of Sphingolipid's by targeting a ceramide synthase unique to fungi.

Tylactone synthase or TYLS is a Type 1 polyketide synthase. TYLS is found in strains of Streptomyces fradiae and responsible for the synthesis of the macrolide ring, tylactone, the precursor of an antibiotic, tylosin. TYLS is composed of five large multi-functional proteins, TylGI-V. Each protein contains either one or two modules. Each module consists of a minimum of a Ketosynthase (KS), an Acyltransferase (AT), and an Acyl carrier protein (ACP) but may also contain a Ketoreductase (KR), Dehydrotase (DH), and Enoyl Reductase (ER) for additional reduction reactions. The domains of TYLS have similar activity domains to those found in other Type I polyketide synthase such as 6-Deoxyerythronolide B synthase (DEBS). The TYLS system also contains a loading module consisting of a ketosynthase‐like decarboxylase domain, an acyltransferase, and acyl carrier protein. The terminal Thioesterase terminates tylactone synthesis by cyclizing the macrolide ring. After the TYLS completes tylactone synthesis, the tylactone molecule is modified by oxidation at C-20 and C-23 and glycosylation of mycaminose, mycinose, and mycarose to produce tylosin.

Andrimid is an antibiotic natural product that is produced by the marine bacterium Vibrio coralliilyticus. Andrimid is an inhibitor of fatty acid biosynthesis by blocking the carboxyl transfer reaction of acetyl-CoA carboxylase (ACC).

<span class="mw-page-title-main">Pladienolide B</span> Chemical compound

Pladienolide B is a natural product produced by bacterial strain, Streptomyces platensis MER-11107, which is a gram-positive bacteria isolated from soil in Japan. Pladienolide B is a molecule of interest due to its potential anti-cancer properties. Its anti-cancer mode of action includes binding to the SF3B complex in the U2 snRNP in the human spliceosome.

References

  1. ↑ IUPAC , Compendium of Chemical Terminology , 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) " Polyketides ". doi : 10.1351/goldbook.P04734
  2. ↑ Collie N, Myers WS (1893). "VII.—The formation of orcinol and other condensation products from dehydracetic acid". Journal of the Chemical Society, Transactions. 63: 122–128. doi:10.1039/CT8936300122. ISSN   0368-1645.
  3. ↑ Collie JN (1907). "CLXXI.—Derivatives of the multiple keten group". Journal of the Chemical Society, Transactions. 91: 1806–1813. doi:10.1039/CT9079101806. ISSN   0368-1645.
  4. 1 2 3 Smith S, Tsai SC (October 2007). "The type I fatty acid and polyketide synthases: a tale of two megasynthases". Natural Product Reports. 24 (5): 1041–1072. doi:10.1039/B603600G. PMC   2263081 . PMID   17898897.
  5. ↑ Birch AJ, Massy-Westropp RA, Moye CJ (1955). "Studies in relation to biosynthesis. VII. 2-Hydroxy-6-methylbenzoic acid in Penicillium griseofulvum Dierckx". Australian Journal of Chemistry. 8 (4): 539–544. doi:10.1071/ch9550539. ISSN   1445-0038.
  6. ↑ Lane AL, Moore BS (February 2011). "A sea of biosynthesis: marine natural products meet the molecular age". Natural Product Reports. 28 (2): 411–428. doi:10.1039/C0NP90032J. PMC   3101795 . PMID   21170424.
  7. ↑ Johnston C, Ibrahim A, Magarvey N (2012-08-01). "Informatic strategies for the discovery of polyketides and nonribosomal peptides". MedChemComm. 3 (8): 932–937. doi:10.1039/C2MD20120H. ISSN   2040-2511.
  8. ↑ Pfeifer BA, Khosla C (March 2001). "Biosynthesis of polyketides in heterologous hosts". Microbiology and Molecular Biology Reviews. 65 (1): 106–118. doi:10.1128/MMBR.65.1.106-118.2001. PMC   99020 . PMID   11238987.
  9. 1 2 Gomes ES, Schuch V, de Macedo Lemos EG (December 2013). "Biotechnology of polyketides: new breath of life for the novel antibiotic genetic pathways discovery through metagenomics". Brazilian Journal of Microbiology. 44 (4): 1007–1034. doi:10.1590/s1517-83822013000400002. PMC   3958165 . PMID   24688489.
  10. 1 2 Voet D, Voet JG, Pratt CW (2013). Fundamentals of Biochemistry: Life at the Molecular Level (4th ed.). John Wiley & Sons. p. 688. ISBN   9780470547847.
  11. ↑ Staunton J, Weissman KJ (August 2001). "Polyketide biosynthesis: a millennium review". Natural Product Reports. 18 (4): 380–416. doi:10.1039/a909079g. PMID   11548049.
  12. ↑ Moore BS, Hertweck C (February 2002). "Biosynthesis and attachment of novel bacterial polyketide synthase starter units". Natural Product Reports. 19 (1): 70–99. doi:10.1039/B003939J. PMID   11902441.
  13. ↑ Wang J, Zhang R, Chen X, et al. (May 2020). "Biosynthesis of aromatic polyketides in microorganisms using type II polyketide synthases". Microbial Cell Factories. 19 (1): 110. doi: 10.1186/s12934-020-01367-4 . PMC   7247197 . PMID   32448179.
  14. ↑ Moretto L, Heylen R, Holroyd N, et al. (February 2019). "Modular type I polyketide synthase acyl carrier protein domains share a common N-terminally extended fold". Scientific Reports. 9 (1): 2325. Bibcode:2019NatSR...9.2325M. doi:10.1038/s41598-019-38747-9. PMC   6382882 . PMID   30787330.
  15. 1 2 Walsh C, Tang Y (2017). Natural product biosynthesis. Royal Society of Chemistry. ISBN   978-1-78801-131-0. OCLC   985609285.
  16. ↑ Risdian C, Mozef T, Wink J (May 2019). "Biosynthesis of Polyketides in Streptomyces". Microorganisms. 7 (5): 124. doi: 10.3390/microorganisms7050124 . PMC   6560455 . PMID   31064143.
  17. ↑ Robinson JA (May 1991). "Polyketide synthase complexes: their structure and function in antibiotic biosynthesis". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 332 (1263): 107–114. Bibcode:1991RSPTB.332..107R. doi:10.1098/rstb.1991.0038. PMID   1678529.
  18. ↑ Noar RD, Daub ME (2016-07-07). "Bioinformatics Prediction of Polyketide Synthase Gene Clusters from Mycosphaerella fijiensis". PLOS ONE. 11 (7): e0158471. Bibcode:2016PLoSO..1158471N. doi: 10.1371/journal.pone.0158471 . PMC   4936691 . PMID   27388157.
  19. ↑ Katz L (November 1997). "Manipulation of Modular Polyketide Synthases". Chemical Reviews. 97 (7): 2557–2576. doi:10.1021/cr960025+. PMID   11851471.
  20. ↑ Shen B (April 2003). "Polyketide biosynthesis beyond the type I, II and III polyketide synthase paradigms". Current Opinion in Chemical Biology. 7 (2): 285–295. doi:10.1016/S1367-5931(03)00020-6. PMID   12714063.
  21. 1 2 Nivina A, Yuet KP, Hsu J, Khosla C (December 2019). "Evolution and Diversity of Assembly-Line Polyketide Synthases". Chemical Reviews. 119 (24): 12524–12547. doi:10.1021/acs.chemrev.9b00525. PMC   6935866 . PMID   31838842.
  22. ↑ "5.13E: Polyketide Antibiotics". Biology LibreTexts. 2017-05-09. Retrieved 2021-07-05.
  23. 1 2 Ross C, Opel V, Scherlach K, Hertweck C (December 2014). "Biosynthesis of antifungal and antibacterial polyketides by Burkholderia gladioli in coculture with Rhizopus microsporus". Mycoses. 57 (Suppl 3): 48–55. doi: 10.1111/myc.12246 . PMID   25250879.
  24. ↑ Jiang L, Pu H, Xiang J, et al. (2018). "Huanglongmycin A-C, Cytotoxic Polyketides Biosynthesized by a Putative Type II Polyketide Synthase From Streptomyces sp. CB09001". Frontiers in Chemistry. 6: 254. Bibcode:2018FrCh....6..254J. doi: 10.3389/fchem.2018.00254 . PMC   6036704 . PMID   30013965.
  25. ↑ Chan YA, Podevels AM, Kevany BM, Thomas MG (January 2009). "Biosynthesis of polyketide synthase extender units". Natural Product Reports. 26 (1): 90–114. doi:10.1039/b801658p. PMC   2766543 . PMID   19374124.
  26. ↑ Kim HJ, Choi SH, Jeon BS, et al. (December 2014). "Chemoenzymatic synthesis of spinosyn A". Angewandte Chemie. 53 (49): 13553–13557. doi:10.1002/anie.201407806. PMC   4266379 . PMID   25287333.
  27. ↑ Rimando AM, Baerson SR, eds. (2007-01-11). Polyketides: Biosynthesis, Biological Activity, and Genetic Engineering. ACS Symposium Series. Vol. 955. Washington, DC: American Chemical Society. doi:10.1021/bk-2007-0955.ch001. ISBN   978-0-8412-3978-4.
  28. ↑ Weissman K, Leadlay B (2005). "Combinatorial biosynthesis of reduced polyketides". Nature Reviews Microbiology . 3 (12): 925–936. doi:10.1038/nrmicro1287. PMID   16322741. S2CID   205496204.
  29. ↑ Brockmann H, Henkel W (1951). "Pikromycin, ein bitter schmeckendes Antibioticum aus Actinomyceten" [Pikromycin, a bitter tasting antibiotic from an actinomycete]. Chem. Ber. (in German). 84 (3): 284–288. doi:10.1002/cber.19510840306.
  30. ↑ Gagne SJ, Stout JM, Liu E, et al. (July 2012). "Identification of olivetolic acid cyclase from Cannabis sativa reveals a unique catalytic route to plant polyketides". Proceedings of the National Academy of Sciences of the United States of America. 109 (31): 12811–12816. Bibcode:2012PNAS..10912811G. doi: 10.1073/pnas.1200330109 . PMC   3411943 . PMID   22802619.
  31. ↑ Li S, Yang B, Tan GY, et al. (June 2021). "Polyketide pesticides from actinomycetes". Current Opinion in Biotechnology. Chemical Biotechnology ● Pharmaceutical Biotechnology. 69: 299–307. doi:10.1016/j.copbio.2021.05.006. PMID   34102376. S2CID   235378697.
  32. ↑ Caro Y, Venkatachalam M, Lebeau J, et al. (2016). "Pigments and Colorants from Filamentous Fungi". In Merillon JM, Ramawat KG (eds.). Fungal Metabolites. Reference Series in Phytochemistry. Cham: Springer International Publishing. pp. 1–70. doi:10.1007/978-3-319-19456-1_26-1. ISBN   978-3-319-19456-1.
  33. ↑ Tauchen J, Huml L, Rimpelova S, Jurášek M (August 2020). "Flavonoids and Related Members of the Aromatic Polyketide Group in Human Health and Disease: Do They Really Work?". Molecules. 25 (17): 3846. doi: 10.3390/molecules25173846 . PMC   7504053 . PMID   32847100.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.